polymers

Article Enhancement of Microcapsules by Using Two Biopolymers as Wall Materials

Chuntao Xu 1,2 , Xuemin Zeng 3, Zujin Yang 4,* and Hongbing Ji 1,3,4,5,*

1 School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China; [email protected] 2 School of Information Engineering, Zhongshan Polytechnic, Zhongshan 528400, China 3 Fine Chemical Industry Research Institute, School of Chemistry, Yat-Sen University, Guangzhou 510275, China; [email protected] 4 School of Chemical Engineering and Technology, Sun Yat-Sen University, Zhuhai 519082, China 5 School of Chemical Engineering, Guangdong University of Petrochemical Technology, Maoming 525000, China * Correspondence: [email protected] (Z.Y.); [email protected] (H.J.)

Abstract: Octyl methoxycinnamate (OMC) is widely used as a chemical sunscreen in sunscreen cosmetics. However, its direct contact with the skin would bring certain risks, such as skin photo- sensitive reaction. How to improve the effect of skin photodamage protection has become a current research hotspot. Encapsulating (UV) filters into microcapsules is an interesting method to increase the photostability of filters. In this study, sodium caseinate (SC) and arabic gum (GA) are chosen as wall materials to prepare synergistic sunscreen microcapsules by complex coacervation technology. A series of experiments are conducted to investigate the effects of pH, wall material   concentration, and wall/core ratio on the formation of OMC microcapsules. The morphology, com- position, and stability of OMC microcapsules are characterized by scanning electron microscopy Citation: Xu, C.; Zeng, X.; Yang, Z.; Ji, (SEM), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). The H. Sunscreen Enhancement of Octyl OMC microcapsule is uniform in size distribution, smooth in surface morphology, and has good Methoxycinnamate Microcapsules by thermal stability. The results show that the ultraviolet absorption of the OMC microcapsules is better Using Two Biopolymers as Wall than that of the uncoated OMC for the ultraviolet-B (280–320 nm). Moreover, the OMC microcapsule Materials. Polymers 2021, 13, 866. https://doi.org/10.3390/ released 40% in 12 h, while OMC released 65%, but the sun protection factor (SPF) of the OMC polym13060866 microcapsule sunscreen is 18.75% higher than that of OMC. This phenomenon may be attributed to the hydrophobic interaction between SC and OMC and the electrostatic interaction between SC Academic Editor: Alina Sionkowska and GA.

Received: 1 February 2021 Keywords: octyl methoxycinnamate; sunscreen; microcapsule; complex coacervation; synergistic Accepted: 8 March 2021 effects Published: 11 March 2021

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in 1. Introduction published maps and institutional affil- In recent decades, the destruction of the atmospheric layer has made people iations. suffer from excess of ultraviolet (UV) radiation, causing serious damage to the human health [1,2]. It has been reported that about 1.5 million disability-adjusted life years (DALYS) in the world were related to UV radiation [3]. Based on the wavelength and energy, UV radiations are mainly divided into three bands: short-wave ultraviolet Copyright: © 2021 by the authors. C (UVC, 100–280 nm), medium-wave ultraviolet B (UVB, 280–320 nm), and long-wave Licensee MDPI, Basel, Switzerland. ultraviolet A (UVA, 320–400 nm), respectively [4,5]. UVC with the weakest penetration This article is an open access article force could be completely absorbed by the atmosphere, but 5–10% of UVB and 90–95% distributed under the terms and of UVA radiation could penetrate the clouds and the ozone layer to the earth surface, conditions of the Creative Commons causing harm to our skin [6,7]. For example, UVB overexposure to skin would lead Attribution (CC BY) license (https:// to inflammation, immunosuppression, and [8]. Therefore, it is particularly creativecommons.org/licenses/by/ important to effectively avoid UVB absorption in life. Some methods have been used 4.0/).

Polymers 2021, 13, 866. https://doi.org/10.3390/polym13060866 https://www.mdpi.com/journal/polymers Polymers 2021, 13, x FOR PEER REVIEW 2 of 18

Polymers 2021, 13, 866 2 of 17

effectively avoid UVB absorption in life. Some methods have been used to protect our skin toincluding protect our physical skin including or chemical physical filters oror chemicalabsorbing filters and reflecting or absorbing UV andradiation reflecting [9]. Sun- UV radiationscreen products [9]. Sunscreen are the productsmain skin are pr theotection main against skin protection the damage against of UVB. the damage of UVB. Currently,Currently, octyloctyl methoxycinnamatemethoxycinnamate (OMC)(OMC) isis oneone ofof the the most most common common sunscreen sunscreen agentsagents in in commercially commercially available available cosmetics cosmetics in in the the market market to to resist resist UVB UVB in in sunlight sunlight owing owing toto itsits excellentexcellent UVUV absorptionabsorption curve,curve, highhigh lipophilicity,lipophilicity, andand goodgood oiloil solubilitysolubility [[10,11].10,11]. However,However, during during its its use, use, there there has has been been some some disadvantages disadvantages such such as as poor poor photostability photostability andand strongstrong permeabilitypermeability [12[12].]. AccordingAccording toto previousprevious reports,reports, thethe largelarge amount amount of of OMC OMC wouldwould accumulate accumulate inin thethe deeperdeeper layerslayers ofof skinskin afterafter coatingcoating onon thethe skinskin superficialsuperficial areas.areas. OMCOMC maymay inhibit the the deiodinase deiodinase activity, activity, indu inducece morphological morphological changes changes in the inthe testes testes and andovaries ovaries of rats of rats[13–15], [13– 15and], andaffect affect secretion secretion of estrogen, of estrogen, reproductive reproductive development, development, and andnervous nervous system system of rat of offspring rat offspring [16]. [16Recently]. Recently,, efforts efforts have have been beenmade made to develop to develop some somemore moreefficient efficient and safe and sunscreen safe sunscreen agents, agents, reducing reducing the toxicological the toxicological risk from risk the from percu- the percutaneoustaneous absorption. absorption. In order In order to achieve to achieve this this goal, goal, many many strategies strategies have have been been employed employed to toprevent prevent photodamage photodamage to skin to skin [17]. [17 Microencap]. Microencapsulationsulation is a new is a inclusion new inclusion method method where whereactive activematerials materials are encapsulated are encapsulated in the microcapsules. in the microcapsules. By changing By changing the wall materials, the wall materials,the microcapsules the microcapsules can effectively can effectively protect and protect control and controlrelease releaseof the enclosed of the enclosed active active ingre- ingredientsdients [18–21]. [18– 21It ].was It was a promising a promising technolo technologygy to to encapsulate encapsulate OMC OMC for overcomingovercoming thethe trans-epidermaltrans-epidermal penetration penetration and and promoting promoting UV UV absorption absorption ability. ability. Complex Complex coacervation, coacerva- astion, one as kind one ofkind microencapsulation of microencapsulation technology, technology, is accomplished is accomplished by phase by phase separation separation of oneof one or many or many hydrocolloids hydrocolloids from from the initialthe initial solution solution and and the subsequentthe subsequent deposition deposition of the of newlythe newly formed formed coacervate coacervate phase phase around around the active the ingredientactive ingredient which haswhich been has used been widely used to microencapsulate the active components [22–25]. widely to microencapsulate the active components [22–25]. In the present study, sodium caseinate (SC) and arabic gum (GA) are chosen as In the present study, sodium caseinate (SC) and arabic gum (GA) are chosen as wall wall material to prepare OMC microcapsules based on the complex coacervation method material to prepare OMC microcapsules based on the complex coacervation method (Scheme1). The process conditions of the microcapsules were optimized by adjusting pH, (Scheme 1). The process conditions of the microcapsules were optimized by adjusting pH, wall material concentration, and wall/core ratio. Scanning electron microscopy (SEM), wall material concentration, and wall/core ratio. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA) are Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA) used to characterize the morphology, structures, and stability of the OMC microcapsules. are used to characterize the morphology, structures, and stability of the OMC microcap- Finally, the encapsulation efficiency, release, and sun protection performance of the OMC sules. Finally, the encapsulation efficiency, release, and sun protection performance of the microcapsules are also investigated. OMC microcapsules are also investigated.

SchemeScheme 1. 1.Preparation Preparation of of octyl octyl methoxycinnamate methoxycinnamate (OMC) (OMC) microcapsule microcapsule by by complex complex coacervation. coacervation.

Polymers 2021, 13, 866 3 of 17

2. Materials and Methods 2.1. Materials and Reagents The sunscreen octyl methoxycinnamate (OMC) was purchased from Shanghai Al- addin Bio-Chemistry Technology Co., Ltd. (Shanghai, China). Sodium caseinate (SC) was supplied by Shanghai Jiecong Trading Co., Ltd. (Shanghai, China). Arabic gum (GA) was obtained from Guangzhou Zhuoxin Bio-s Co., Ltd. (Guangzhou, China). Glacial acetic and glutaraldehyde were provided by Shenzhen Yinuo Food Ingredients Co., Ltd. (Shenzhen, China) and Guangzhou Mingwang Biotechnology Co., Ltd. (Guangzhou, China), respectively. Other chemicals and solvents used in this work were of analytical grade and purified by general methods.

2.2. Selection of Wall Materials In order to obtain sunscreen-loaded microcapsules with good sunscreen effect, it was necessary to study the OMC microcapsules by using the different wall materials with the good ultraviolet absorption. Several kinds of wall materials, such as modified starch (C001), sodium carboxymethyl cellulose (CMC), arabic gum (GA), sodium alginate (ALG), chitosan (CS), sodium caseinate (SC), maltodextrin (MD), and β-cyclodextrin (β-CD), were measured by UV spectrophotometer (LC-16, Shimadzu, Kyoto, Japan) during 200–400 nm.

2.3. Preparation of OMC Microcapsules In this study, the complex coacervation method was used to prepare OMC micro- capsules as follows: a series of SC or GA solutions (1.0%) were obtained by dissolved SC or GA in the buffered solutions with different pH values (2.5, 3.0, 3.5, 4.0, 4.5, and 5.0). Then, the zeta potentials of solutions were measured by dynamic light scattering (DLS, Malvern Instruments, Worcestershire, UK). According to the values of the zeta potentials, the theoretical strength of electrostatic interactions (SEI) was calculated as:

SEI = |Z1| × |Z2| (1)

where Z1 and Z2 represent the zeta potential of SC and GA, respectively. Dissolving 0.3 g OMC in 15 mL SC solutions (1.0%, w/w). After homogenizing at 50 ◦C for 5 min, the mixture was added into a series of 1.0% GA solutions (1.5, 3.0, 6.0, 8.0, 12.0, 15.0, 18.0, and 24.0 mL). After stirring at 500 rpm for 2 h (RW20, IKA, Shanghai, China), glacial acetic acid was added to the above solution dropwise to adjust the pH of solutions to a certain value (2.5, 3.0, 3.5, and 4.0). The obtained solutions were stirred at 500 rpm for 2 h at room temperature. The samples were dried under vacuum with a freeze dryer (Martin Christ GmbH, Osterode am Harz, Germany) to obtain OMC microcapsules. The amount of OMC in the OMC microcapsules was determined by high-performance liquid chromatography at λ = 310 nm (HPLC, LC-16, Agilent, Santa Clara, CA, USA)), detected at a wavelength of 310 nm, and calculated by drawing the standard curve of OMC. Each experiment was performed in triplicate and standard deviation was used as the error bars.

The amount of OMC in the microcapsules LC (%) = × 100 (2) The total microcapsules

The amount of OMC in the microcapsules EE (%) = × 100 (3) The total OMC

2.4. Experimental Designs of OMC Microcapsules The factors that may affect encapsulation efficiency of OMC microcapsules were studied mostly by using an orthogonal experiment, and they included stirring speed, ratio of wall material to core material, and content of curing agent. Then, the factors that influence the characteristics of hydrothermal products were selected on the basis of the same experiment to conduct the single-factor test. The current study mainly identified encapsulation efficiency of OMC microcapsules at stirring speed ranging between 200 and Polymers 2021, 13, 866 4 of 17

400 rpm, with a ratio of wall material to core material ranging from 1:2 to 2:1 and content of curing agent of 1–3%. The experimental conditions are displayed in Table1.

Table 1. Summary of experimental conditions.

Ratio of Core Material Curing Agent Stirring Speed to Wall Material Content 200 1:2 1% Orthogonal 400 1:1 2% 600 2:1 3%

2.5. Characterization of OMC Microcapsules The mean size, size distribution, and the zeta potential of the OMC microcapsules were recorded by DLS with a Zetasizer Nano ZS (Malvern Instruments, Worcestershire, UK). The average diameters and size distributions were acquired by measuring 100 droplets individually (Image J software, National Institutes of Health, Bethesda, MD, USA), for which the model is expressed as: ∑ nd DnL = (4) ∑ n The morphology of OMC microcapsules was observed by a Hitachi S-520 scanning electron microscope (SEM, Hitachi, Tokyo, Japan) with accelerating voltage of 15 kV. FTIR spectra (Bruker TENSOR II, Karlsruhe, Germany) were used to analyze the structure of the test samples in the wavelength range of 4000–400 cm−1 at 4.0 cm−1 resolution. The thermal stability of OMC, SC, and GA complex and OMC microcapsules was determined by using a NETZSCH STA 449C thermal analysis system (Selb, Germany).

2.6. Release of OMC from the OMC Microcapsules The release of OMC from the microcapsules was also investigated using the dialy- sis method [26,27], with some modification. Briefly, 10 mg of OMC microcapsules was dissolved in 5 mL of phosphate-buffered solution (PBS) at pH = 6.5 under ultrasonic ir- radiation (KQ-400DE, Kunshan, China). 1 mL of solution was sampled and diluted to 4 mL with PBS, and dialyzed with 30 mL of the PBS by using a dialysis tube (molecular weight cut-off (MWCO): 3500 Da) at 37 ◦C. At predetermined time intervals, 0.5 mL of release media was withdrawn and the same volume of fresh PBS was added. The amount of released OMC was determined by the HPLC (λ = 310 nm). For comparison, the release of free OMC without SC and GA complex was performed in the same condition [22]. The cumulative releases were calculated as,

n−1 (Ve ∑ Ci + V0Cn) × 100 Release(%) = 0 (5) m

where V0, Cn, Ve, Ci, and m represented the total volume of outside solutions, the concen- tration of OMC at time n, the volume taken out each time, the concentration of OMC at time of i, and the total mass of OMC at the beginning, respectively. Mathematical model of OMC release is an efficient method to understand the deliv- ery of bioactive molecules, which can understand factors affecting the release rate and reduce the number of experiments. The release behavior of the OMC microcapsule was investigated by four kinds of kinetics mode, including zero order, first order, Higuchi, and Rigter-Peppas model to obtain the best kinetics mode based on the highest R2,

R t = kt (6) R∞ R t = 1 − e−kt (7) R∞ Polymers 2021, 13, 866 5 of 17

R t = kt1/2 (8) R∞ R t = ktn (9) R∞

where Rt is the release amounts of OMC at t, R∞ is the total release amounts of OMC at infinite time, Rt/R∞ is the fraction of OMC released at t, and k is a constant, respectively. Exponent n is usually used to characterize four types of transport of active molecules through the matrix [7], which describes the kinetic and mechanism of OMC release. When n ≤ 0.43, the major driving force is the Fickian diffusion, if n is in the range of 0.43 and 0.85, the release mechanism is the diffusion and the swelling and n = 0.85 indicates zero order release kinetics, and n > 0.85 demonstrates Super Case-II transport [24].

2.7. UV Absorption Effect of the OMC Microcapsules According to “The evaluation method of sunscreen effect of sunscreen cosmetic-UV absorbance method”, the sunscreen performance of the OMC microcapsules was tested by an UV/vis near-infrared spectrophotometer (UV-3600 Plus, Shimadzu, Kyoto, Japan), and its wavelength was from 200 to 800 nm. In detail, the same content of sunscreen and the OMC microcapsules were smeared on the 3 M tape and further scanned from 280 to 400 nm. Finally, the UV absorption map was drawn.

2.8. Test of Sun Protection Factor (SPF) Value The OMC microcapsules were used to test its sunscreen ability and sustained-release performance according to the reported method [25]. The sunscreen formulations were prepared according to the 2015 edition “cosmetic safety technical guide” (Table2), as follows: phase A and phase B are heated to 75–80 ◦C respectively, and stirred continuously until all the components are dissolved, and until the liquid becomes clear when necessary. Phase C is added to the mixture of phase A and phase B, heated to 75–80 ◦C, stirred homogeneously with high shear dispersion emulsifier (RW20, IKA, Shanghai, China), and then neutralized with lactic acid or sodium hydroxide. Finally, the mixture was cooled to room temperature, and used to test the SPF value of sunscreen products in vitro. Four samples (sunscreen of OMC, sunscreen of OMC microcapsules, mixed sunscreen, and sunscreen from market) of SPF value were tested by SPF-290AS (Solarlight, Glenside, PA, USA) in vitro. Each experiment was performed in triplicate and standard deviation was used as the error bars.

Table 2. Sunscreen formula tested in the experiments.

Components Mass Fraction (%) Phase A Cetearyl Alcohol 2.21 PEG-40 Castor oil 0.63 Sodium Cetearyl Sulphate 0.32 Decyl Oleate 15.00 Ethylhexyl Methoxycinnamate 3.00 Butyl Methoxydibenzoylmethane 0.50 Propylparaben 0.10 Phase B Water 53.57 2-Phenyl-Benzimidazole-5-Sulphonic Acid 2.78 Sodium Hydroxide (45% solution) 0.90 Methylparaben 0.30 Disodium Ethylene Diamine Tetraacetic Acid (EDTA) 0.10 Phase C Water 20.00 Carbomer 0.30 Sodium Hydroxide (45% solution) 0.30 Polymers 2021, 13, 866 6 of 17

2.9. Statistical Analysis The results were evaluated according to the analysis of variance (ANOVA), and the means were compared by the Tukey test, considering the significance level of 5% (p < 0.05), using Statistica 7 software (StatSoft, Tulsa, OK, USA).

3. Results and Discussion 3.1. Screening of Natural Polymer Wall Materials As shown in Figure1, the absorbance of the different wall materials was different in UVB (280–320 nm), and the order of UV absorption was SC > CS > ALG > GA > C001 = CMC > MD = β-CD. In this region (280–320 nm), SC has the highest UV absorbance. It is attributed that SC is composed of α-, β-, γ-, and κ-casein, which contain a large number of aromatic amino such as tyrosine and tryptophan, which have a relatively large conjugated structure in the molecule with a strong absorption peak around 280 nm. Therefore, it has been used as one of the wall materials of sunscreen microcapsules. CS also has good UV absorption, because CS is mainly composed of amino-D-glucose and N-acetyl- D-glucosamine, with a certain number of double bonds in the molecule and relatively high absorbance. However, CS is an acid-soluble substance (pH < 6) and can dissolve in the buffer solution (pH < 5). This pH is close to the isoelectric point of SC, and the pH range of the two for complex coagulation is too small, so it is not suitable for the wall material for the complex coagulation experiment. The ultraviolet absorption of ALG and GA is similar. Compared with ALG, GA has better solubility and lower viscosity, which is beneficial to the fluidity and dispersity of the capsule. Through comprehensive comparison, SC Polymers 2021, 13, x FOR PEER REVIEW 7 of 18 and GA were selected as wall materials to prepare sunscreen microcapsules by complex coacervation.

4.5 —— C001 —— CMC —— GA —— ALG 3.0 —— CS —— SC —— MD

Absorbance 1.5 —— β-CD

0.0 200 250 300 350 400 Wavelength (nm) . FigureFigure 1.1. UltravioletUltraviolet (UV)(UV) absorptionabsorption effecteffect ofof wallwall material.material. 3.2. Preparation of the OMC Microcapsules 3.2. Preparation of the OMC Microcapsules The zeta potentials of GA and SC at different pH are studied by DLS. As shown in The zeta potentials of GA and SC at different pH are studied by DLS. As shown in Figure2, GA solutions showed zeta potentials, and the negative charges increased with Figure 2, GA solutions showed zeta potentials, and the negative charges increased with increasing the pH from 2.5 to 5, which were due to the ionization of carboxyl groups in GA inincreasing acid environment. the pH from SC 2.5 solutions to 5, which showed were positive due to zetathe ionization potentials whenof carboxyl pH < groups 4.5, were in closeGA in to acid 0 when environment. pH was 4.5, SC but solutions they were showed negative positive when zeta pH potentials > 4.5. The when significant pH < pH4.5, changeswere close in SCto 0 solution when pH were was due 4.5, to but the presencethey were of negative some carboxyl when pH and > amine 4.5. The groups significant in SC. WhenpH changes pH < 4.5,in SC SC solution solution were showed due positive to the presence zeta potentials of some due carboxyl to the protonatedand amine groups amine groups,in SC. When and negative pH < 4.5, zeta SC solution potentials showed when pHpositive > 4.5, zeta which potentials was ascribed due toto the the protonated carboxyl groupamine ionization,groups, and and negative the zeta zeta potential potentials of SC when was close pH to> 4.5, zero which when thewas equal ascribed groups to the of aminecarboxyl and group carboxyl ionization, protonated and the or ionizationzeta potential were of at SC isoelectric was close point to zero [26 ].when As shown the equal in Figuregroups2, of the amine maximum and carboxylSEI value protonated appeared ator pH ionization = 4.0, implying were at the isoelectric strongest point electrostatic [26]. As shown in Figure 2, the maximum SEI value appeared at pH = 4.0, implying the strongest electrostatic interaction between SC and GA. However, the lowest SEI value was observed when pH of the solutions of SC and GA was at 2.5.

350 30 SEI CS GA 300 20 250 ) Zeta (mV)

2 10 200 (mV 0

SEI 150 -10 100

50 -20

0 -30 2.5 3.0 3.5 4.0 4.5 5.0 pH

Figure 2. The zeta potentials (mV) and SEI (mV2) measurement of the GA and SC in different pH values. Means of values obtained in triplicate (p ≤ 0.05).

The OMC microcapsules were prepared by the complex coacervation method with SC and GA as wall materials and OMC as core materials at different pH. Figure 3 shows

Polymers 2021, 13, x FOR PEER REVIEW 7 of 18

4.5 —— C001 —— CMC —— GA —— ALG 3.0 —— CS —— SC —— MD

Absorbance 1.5 —— β-CD

0.0 200 250 300 350 400 Wavelength (nm) . Figure 1. Ultraviolet (UV) absorption effect of wall material.

3.2. Preparation of the OMC Microcapsules The zeta potentials of GA and SC at different pH are studied by DLS. As shown in Figure 2, GA solutions showed zeta potentials, and the negative charges increased with increasing the pH from 2.5 to 5, which were due to the ionization of carboxyl groups in GA in acid environment. SC solutions showed positive zeta potentials when pH < 4.5, were close to 0 when pH was 4.5, but they were negative when pH > 4.5. The significant pH changes in SC solution were due to the presence of some carboxyl and amine groups in SC. When pH < 4.5, SC solution showed positive zeta potentials due to the protonated amine groups, and negative zeta potentials when pH > 4.5, which was ascribed to the carboxyl group ionization, and the zeta potential of SC was close to zero when the equal Polymers 2021, 13, 866 groups of amine and carboxyl protonated or ionization were at isoelectric point [26]. As7 of 17 shown in Figure 2, the maximum SEI value appeared at pH = 4.0, implying the strongest electrostatic interaction between SC and GA. However, the lowest SEI value was observed wheninteraction pH of the between solutions SC of and SC GA. and However,GA was at the 2.5. lowest SEI value was observed when pH of the solutions of SC and GA was at 2.5.

350 30 SEI CS GA 300 20 250 ) Zeta (mV)

2 10 200 (mV 0

SEI 150 -10 100

50 -20

0 -30 2.5 3.0 3.5 4.0 4.5 5.0 pH

Figure 2. The zeta potentials (mV) and SEI (mV2) measurement of the GA and SC in different pH Figure 2. The zeta potentials (mV) and SEI (mV2) measurement of the GA and SC in different pH values. Means of values obtained in triplicate (p ≤ 0.05). values. Means of values obtained in triplicate (p ≤ 0.05). The OMC microcapsules were prepared by the complex coacervation method with SCThe and OMC GA asmicrocapsules wall materials were and prepared OMC as coreby the materials complex at coacervation different pH. method Figure3 with shows SC andthe morphologyGA as wall materials of the OMC and OMC microcapsules as core materials by metalloscope. at different FigurepH. Figure3a shows 3 shows many oil droplets with different particle sizes, suggesting the failed preparation of the OMC microcapsules at pH = 4.0. It could be seen from Figure3b that OMC was encapsulated

by SC and GA as wall materials with dendritic shape, suggesting that some OMC were included in the core of GA/SC wall materials at pH = 3.5. From Figure3c, OMC was encapsulated by SC and GA with dendritic shape, implying the preparation of the OMC microcapsules at pH = 3.0. As shown in Figure3d, the spherical microcapsules were observed with core-shell structure, indicating that the OMC microcapsules were prepared successfully at pH = 2.5. The phenomenon was mainly due to the electrostatic interaction between SC and GA [27]. The higher pH (2.5–4.0) was not conducive to the formation of the OMC microcapsules due to the stronger electrostatic interaction between SC and GA. The optimized pH of the OMC microcapsules with different ratios of SC and GA as wall materials was 2.5 in this study. Ratio of mixture of GA/SC is important for the charge balance and the intensity, and the degree of self-aggregation during complexation. Ratio of SC and GA on the coacervation were further studied and shown in Figure4 and Table3. The zeta potentials were observed to change from positive values to negative values with increasing the content of GA. The zeta potential was close to zero when the ratio of GA and SC was 1:1, indicating that the GA and SC were completely neutralized by each other. The further increased ratio of GA and SC could make the OMC microcapsules solutions have negative zeta potentials [28]. In addition, the greatest coacervate yield was observed at the GA/SC ratio 1:1, and a further increase or decrease of the ratio can decrease the coacervation significantly. Therefore, the optimized ratio of GA and SC was 1:1. When the wall material ratio is 1:1, the mean particle size is 10.01 ± 0.012 µm and the polydispersity index (PDI) is 0.202 ± 0.002. The distribution of capsules was uniform. It was also found by Thaiane et al. [29] that the zeta potential of gelatin and arabic gum and the ratio of 1:1 were determined as the most suitable for microencapsulation, as the best condition for the microcapsule formation. Polymers 2021, 13, x FOR PEER REVIEW 8 of 18

the morphology of the OMC microcapsules by metalloscope. Figure 3a shows many oil droplets with different particle sizes, suggesting the failed preparation of the OMC micro- capsules at pH = 4.0. It could be seen from Figure 3b that OMC was encapsulated by SC and GA as wall materials with dendritic shape, suggesting that some OMC were included in the core of GA/SC wall materials at pH = 3.5. From Figure 3c, OMC was encapsulated by SC and GA with dendritic shape, implying the preparation of the OMC microcapsules at pH = 3.0. As shown in Figure 3d, the spherical microcapsules were observed with core- shell structure, indicating that the OMC microcapsules were prepared successfully at pH = 2.5. The phenomenon was mainly due to the electrostatic interaction between SC and GA [27]. The higher pH (2.5–4.0) was not conducive to the formation of the OMC micro- Polymers 2021, 13, 866 capsules due to the stronger electrostatic interaction between SC and GA. The optimized8 of 17 pH of the OMC microcapsules with different ratios of SC and GA as wall materials was 2.5 in this study.

Polymers 2021, 13, x FOR PEER REVIEW 9 of 18

Figure 3. The picture of SC/GA by complex coacervation at different pH. (a) pH = 4.0, (b) pH = 3.5, Figure 3. The picture of SC/GA by complex coacervation at different pH. (a) pH = 4.0, (b) pH = 3.5, (c) pH = 3.0, (d) pH = 2.5. (c) pH = 3.0, (d) pH = 2.5. Ratio of mixture of GA/SC is important for the charge balance and the intensity, and the degree12 of self-aggregation during complexation. Ratio of SC and GA on the coacerva- tion were further studied and shown in Figure 4 and100 Table 3. The zeta potentials were observed9 to change from positive values to negative values with increasing the content of GA. The zeta potential was close to zero when the ratio80 of GA and SC was 1:1, indicating that the6 GA and SC were completely neutralized by each other. The further increased ratio of GA and SC could make the OMC microcapsules solutions60 have negative zeta potentials [28]. In addition, the greatest coacervate yield was observed at the GA/SC ratio 1:1, and a further3 increase or decrease of the ratio can decrease the coacervation significantly. There- fore,(mV) Zeta the optimized ratio of GA and SC was 1:1. When40 the wall material ratio is 1:1, the mean particle size is 10.01 ± 0.012 μm and the polydispersity index (PDI) is 0.202 ± 0.002. 0 Zeta/mV Coacervate Yield (%) The distribution of capsules Coacervate wa Yields uniform. (%) It was also found20 by Thaiane et al. [29] that the zeta -3potential of gelatin and arabic gum and the ratio of 1:1 were determined as the most suitable for microencapsulation, as the best condition 0for the microcapsule formation. 0.00.30.60.91.21.51.8 GA/SC Ratio

FigureFigure 4. Coacervation 4. Coacervation of SC ofand SC GA and as GAa function as a function of mixing of mixingratio. Zeta ratio. potential Zeta potentialof the OMC of themi- OMC

crocapsulesmicrocapsules were recorded were recorded by dynamic by dynamic light scatte lightring scattering (DLS) with (DLS) a withZetasizer a Zetasizer Nano ZS Nano (Malvern ZS (Malvern Instruments,Instruments, Worcestershire, Worcestershire, UK). UK). Means Means of values of values obtained obtained in triplicate in triplicate (p < (0.05).p < 0.05).

Table 3. Zeta-potential, size, and PDI of particles with different samples ratio of GA and SC.

Sample Zeta (mV) Size (μm) PDI S1 10.09 ± 0.484 15.32 ± 0.457 0.348 ± 0.006 S2 8.47 ± 0.216 14.45 ± 0.289 0.432 ± 0.007 S3 7.14 ± 0.269 13.28 ± 0.305 0.332 ± 0.006 S4 4.43 ± 0.154 12.52 ± 0.401 0.323 ± 0.006 S5 2.93 ± 0.087 11.32 ± 0.232 0.301 ± 0.004 S6 1.56 ± 0.048 10.01 ± 0.012 0.202 ± 0.002 S7 –0.19 ± 0.006 8.32 ± 0.175 0.322 ± 0.003 S8 –0.85 ± 0.026 7.56 ± 0.173 0.345 ± 0.002 S9 –2.18 ± 0.087 5.53 ± 0.143 0.366 ± 0.004 Experiment conditions: S1: GA/SC = 0.1, S2: GA/SC = 0.2, S3: GA/SC = 0.4, S4: GA/SC = 0.6, S5: GA/SC = 0.8, S6: GA/SC = 1, S7: GA/SC = 1.2, S8: GA/SC = 1.4, S9: GA/SC = 1.6.

Emulsion stability is important for the formation of microencapsulation, which was affected by the ratio of emulsifier/core materials, and further influenced the characteristics of the OMC microcapsules. The effect of the ratio of OMC and GA/SC on the preparation of the OMC microcapsules was investigated and shown in Figure 5. From Figure 5, it can be seen that a gradual phase separation occurred, and the pink emulsions were gradually divided into two layers of supernatant and pink precipitation with the decrease of the emulsifier. This phenomenon was mainly caused because: (1) the OMC-loaded micelles may be forced based on the high concentration of emulsifier and dispersed in the solu- tions, and OMC could not be included in GA/SC complex, (2) the contact between SC and OMC increased with the decrease of emulsifier concentration, and the complex conden- sation and settlement of the core material would gradually occur. The content of OMC in the solution was decreased gradually, and the solution became clear from turbidity to clarification. (3) OMC was completely emulsified by GA/SC at the low concentration of emulsifier, leading to the obtained OMC microcapsule by complex coacervation settled at the bottom, and no OMC appeared in the solutions.

Polymers 2021, 13, 866 9 of 17

Table 3. Zeta-potential, size, and PDI of particles with different samples ratio of GA and SC.

Sample Zeta (mV) Size (µm) PDI S1 10.09 ± 0.484 15.32 ± 0.457 0.348 ± 0.006 S2 8.47 ± 0.216 14.45 ± 0.289 0.432 ± 0.007 S3 7.14 ± 0.269 13.28 ± 0.305 0.332 ± 0.006 S4 4.43 ± 0.154 12.52 ± 0.401 0.323 ± 0.006 S5 2.93 ± 0.087 11.32 ± 0.232 0.301 ± 0.004 S6 1.56 ± 0.048 10.01 ± 0.012 0.202 ± 0.002 S7 −0.19 ± 0.006 8.32 ± 0.175 0.322 ± 0.003 S8 −0.85 ± 0.026 7.56 ± 0.173 0.345 ± 0.002 S9 −2.18 ± 0.087 5.53 ± 0.143 0.366 ± 0.004 Experiment conditions: S1: GA/SC = 0.1, S2: GA/SC = 0.2, S3: GA/SC = 0.4, S4: GA/SC = 0.6, S5: GA/SC = 0.8, S6: GA/SC = 1, S7: GA/SC = 1.2, S8: GA/SC = 1.4, S9: GA/SC = 1.6.

Emulsion stability is important for the formation of microencapsulation, which was affected by the ratio of emulsifier/core materials, and further influenced the characteristics of the OMC microcapsules. The effect of the ratio of OMC and GA/SC on the preparation of the OMC microcapsules was investigated and shown in Figure5. From Figure5, it can be seen that a gradual phase separation occurred, and the pink emulsions were gradually divided into two layers of supernatant and pink precipitation with the decrease of the emulsifier. This phenomenon was mainly caused because: (1) the OMC-loaded micelles may be forced based on the high concentration of emulsifier and dispersed in the solutions, and OMC could not be included in GA/SC complex, (2) the contact between SC and OMC increased with the decrease of emulsifier concentration, and the complex condensation and settlement of the core material would gradually occur. The content of OMC in the solution was decreased gradually, and the solution became clear from turbidity to clarification. (3) OMC was completely emulsified by GA/SC at the low concentration of emulsifier, leading Polymers 2021, 13, x FOR PEER REVIEWto the obtained OMC microcapsule by complex coacervation settled at the bottom, and10 of no 18

OMC appeared in the solutions.

FigureFigure 5. 5.Effect Effect of of ratio ratio of of emulsifier/core emulsifier/core materialsmaterials onon thethe formationformation ofof thethe OMCOMC microcapsules.microcapsules.

WallWall materialmaterial is usually used used to to include include the the core core material material in its in structure its structure during during pro- processingcessing and and storage. storage. However, However, high high wall wall material material load load often often resulted resulted in inpoor poor retention. retention. In Inthis this study, study, the the effects effects of of the the concentration concentration of of wall wall material in solutionsolution onon thethe preparationpreparation ofof the the OMC OMC microcapsules microcapsules was was also also investigated investigated and and shown shown in in Figure Figure6 .6. From From Figure Figure6, 6, it it cancan be be seen seen that that the the concentration concentration of of GA/SC GA/SC showedshowed aa significantsignificant effecteffect on on the the formation formation ofof the the OMCOMC microcapsules,microcapsules, in in which which the the concentration concentration of of 1.0% 1.0% offered offered the the spherical spherical shape shape withwith the the uniform uniform size. size. However, However, we we would would not not make make SC SC disperse disperse in GA in GA solutions solutions with with the increasethe increase in the in concentration the concentration of SC/GA, of SC/GA, changing changing charge charge during during the the process process of adjusting of adjust- pHing [ 30pH]. [30]. Too muchToo much charge charge may may lead lead to an to intense an intense reaction, reaction, resulting resulting in the in the appearance appearance of irregularof irregular microcapsules. microcapsules. Therefore, Therefore, the concentrationthe concentration of SC/GA of SC/GA for thefor optimizationthe optimization of the of preparationthe preparation process process of sunscreen-loaded of sunscreen-loaded microcapsules microcapsules was 1.0%, was indicating 1.0%, indicating the important the im- interactionportant interaction between between OMC and OMC SC/GA. and SC/GA.

Figure 6. Effect of wall material concentration on the formation of the OMC microcapsules, recorded by DLS with a Zetasizer Nano ZS with ×400. (a) 1%, (b) 1.2%, (c) 1.4%, (d) 1.6%, (e) 1.8%, (f) 2.0%.

The optimization of the preparation process of the OMC microcapsules was further studied by an orthogonal experiment (Table 4). The influence of curing rate, OMC to GA/SC ratio, and curing agent content on the encapsulation efficiency (EE) of the OMC microcapsules was studied. The results showed that the values of R are in the order of curing agent content (0.670) > curing rate (0.135) > wall-core ratio (0.093), indicating that curling agent content is the most important factor, followed by stirring speed and core material ratio. The results also showed that the lower EE would be found at higher content of curing agent, due to the reversible reaction for the complex coacervation. Therefore, the

Polymers 2021, 13, x FOR PEER REVIEW 10 of 18

Figure 5. Effect of ratio of emulsifier/core materials on the formation of the OMC microcapsules.

Wall material is usually used to include the core material in its structure during pro- cessing and storage. However, high wall material load often resulted in poor retention. In this study, the effects of the concentration of wall material in solution on the preparation of the OMC microcapsules was also investigated and shown in Figure 6. From Figure 6, it can be seen that the concentration of GA/SC showed a significant effect on the formation of the OMC microcapsules, in which the concentration of 1.0% offered the spherical shape with the uniform size. However, we would not make SC disperse in GA solutions with the increase in the concentration of SC/GA, changing charge during the process of adjust- ing pH [30]. Too much charge may lead to an intense reaction, resulting in the appearance Polymers 2021, 13, 866 of irregular microcapsules. Therefore, the concentration of SC/GA for the optimization10 of of 17 the preparation process of sunscreen-loaded microcapsules was 1.0%, indicating the im- portant interaction between OMC and SC/GA.

Figure 6. Effect of wall material concentration on the formation of the OMC microcapsules, recorded by DLS with a Figure 6. Effect of wall material concentration on the formation of the OMC microcapsules, recorded by DLS with a Zetasizer Zetasizer Nano ZS with ×400. (a) 1%, (b) 1.2%, (c) 1.4%, (d) 1.6%, (e) 1.8%, (f) 2.0%. Nano ZS with ×400. (a) 1%, (b) 1.2%, (c) 1.4%, (d) 1.6%, (e) 1.8%, (f) 2.0%. The optimization of the preparation process of the OMC microcapsules was further The optimization of the preparation process of the OMC microcapsules was further studied by an orthogonal experiment (Table 4). The influence of curing rate, OMC to studied by an orthogonal experiment (Table4). The influence of curing rate, OMC to GA/SCGA/SC ratio, ratio, and and curing curing agent agent content content on on the the encapsulation encapsulation efficiency efficiency ( (EEEE)) of of the the OMC OMC microcapsulesmicrocapsules was was studied. studied. The The results results showed showed that that the the values values of of RR areare in in the the order order of of curingcuring agent agent content content (0.670) (0.670) > > curing curing rate rate (0.135) (0.135) > > wall-core wall-core ratio ratio (0.093), (0.093), indicating indicating that that curlingcurling agent agent content content is is the the most most important important factor, factor, followed followed by by stirring stirring speed speed and and core core materialmaterial ratio. ratio. The The results results also also showed showed that that the the lower lower EEEE wouldwould be be found found at at higher higher content content ofof curing curing agent, agent, due due to to the the reversible reversible reacti reactionon for for the the complex complex coacervation. coacervation. Therefore, Therefore, the the optimized preparation process was as follows, 200 rpm, ratio of 1:1 of OMC to GA/SC, and 1% curing agent content. The EE and LC of the OMC microcapsules were 83.3% and 41.7%, respectively.

Table 4. Factors and levels of the OMC microcapsules.

Run Speed (rpm) OMC to GA/SC Ratio (g/g) Curing Agent Content (%) EE (%) 1 200 1:1 1% 83.3 2 200 1:2 2% 32.7 3 200 2:1 3% 53.4 4 400 1:1 2% 21.3 5 400 1:2 3% 38.9 6 400 2:1 1% 54.2 7 600 1:1 3% 61.2 8 600 1:2 1% 63.6 9 600 2:1 2% 22.7 K1 0.387 0.349 0.670 K2 0.252 0.321 0.256 K3 0.288 0.256 0.145 R 0.135 0.093 0.670

3.3. Characterization of the OMC Microcapsules The formation of the OMC microcapsules prepared by the optimized process was confirmed by SEM observation. The outer morphology of the microcapsules is presented in Polymers 2021, 13, x FOR PEER REVIEW 11 of 18

optimized preparation process was as follows, 200 rpm, ratio of 1:1 of OMC to GA/SC, and 1% curing agent content. The EE and LC of the OMC microcapsules were 83.3% and 41.7%, respectively.

Table 4. Factors and levels of the OMC microcapsules.

Run Speed (rpm) OMC to GA/SC Ratio (g/g) Curing Agent Content (%) EE (%) 1 200 1:1 1% 83.3 2 200 1:2 2% 32.7 3 200 2:1 3% 53.4 4 400 1:1 2% 21.3 5 400 1:2 3% 38.9 6 400 2:1 1% 54.2 7 600 1:1 3% 61.2 8 600 1:2 1% 63.6 9 600 2:1 2% 22.7 K1 0.387 0.349 0.670 K2 0.252 0.321 0.256 K3 0.288 0.256 0.145 R 0.135 0.093 0.670 Polymers 2021, 13, 866 11 of 17 3.3. Characterization of the OMC Microcapsules The formation of the OMC microcapsules prepared by the optimized process was Figureconfirmed7. It can by be SEM seen observation. that the microcapsules The outer morphology are bonded toof eachthe microcapsules other, which was is presented common inin the Figure freeze-drying 7. It can processbe seen by that matrix the micr contractocapsules during are the bonded drying processto each [other,29]. The which complete was microcapsulescommon in the can freeze-drying ensure the effective process protection by matrix of contract the encapsulated during the OMC drying (Figure process7a). [29]. The microcapsulesThe complete hadmicrocapsules spherical morphologies can ensure the with effective smooth protection surface of appearance, the encapsulated which OMC were micro-sized,(Figure 7a). andThe themicrocapsules average diameter had spherical was about morphologies 10 µm based with on 100smooth particles surface (Figure appear-7b). Theance, result which of microcapsuleswere micro-sized, was and similar the toaverage the results diameter reported was about by Michele 10 μm et based al. [31 on], and100 theparticles results (Figure are consistent 7b). The with result the of results microcapsules of the metalloscope. was similar to the results reported by Michele et al. [31], and the results are consistent with the results of the metalloscope.

Figure 7. Scanning electron microscopy (SEM) of the microencapsulated OMC. (a) Structure of Figure 7. Scanning electron microscopy (SEM) of the microencapsulated OMC. (a) Structure of microcapsule aggregates, (b) structure of several microcapsules connected together. microcapsule aggregates, (b) structure of several microcapsules connected together. The thermal stability of OMC and GA/SC as wall material and the OMC microcap- The thermal stability of OMC and GA/SC as wall material and the OMC microcapsules sules was investigated by thermogravimetric analysis, as shown in Figure 8. The thermo- was investigated by thermogravimetric analysis, as shown in Figure8. The thermogram for gram for the pure OMC showed one thermal event, at 200–280 °C, which was due to the the pure OMC showed one thermal event, at 200–280 ◦C, which was due to the volatilization volatilization of OMC [32]. The GA/SA had three thermal degradation events, the first of OMC [32]. The GA/SA had three thermal degradation events, the first between 25 ◦C between 25 °C and 150 °C, corresponding to weight loss of the remaining water in the and 150 ◦C, corresponding to weight loss of the remaining water in the sample with a sample with a mass loss of about 15%. Another weight lost was observed from 211.8 °C to mass loss of about 15%. Another weight lost was observed from 211.8 ◦C to 470 ◦C, the temperature range where GA or SA degradation occurs, corresponding to 60% of weight loss. The third weight loss was due to the carbonization process, with 10% of weight loss. The thermal degradation process of the OMC microcapsule presented four thermal events. The first was in the range from 25 to 150 ◦C, with 15% mass loss due to evaporation of water. In the second event (220–300 ◦C), there was a significant mass loss, about 70%, indicating the release of the core material. In the third event (320–420 ◦C), there was a mass loss of about 10%, which was due to the decomposition of GA/SC, and the GA/SC used as wall materials may have caused this high weight loss [33]. The fourth weight loss was due to the carbonization process, with 8% of weight loss. The results showed that the OMC thermal stability was significantly improved by the encapsulation process [34]. This increased thermal stability can be due to the thermal resistance of GA/SA used as a microcapsule casing, resulting in a slower release. FTIR was applied to estimate the interactions of the OMC and SC/GA using OMC and SC/GA as control. FTIR spectra of OMC, GA/SC, and the OMC microcapsules are shown in Figure9 in the range of 4000–500 cm −1. The spectra of all samples, except for free OMC, showed a stretching band at 3420 cm−1 corresponding to –OH groups [9]. For OMC, the strong peaks around 2962 and 2872 cm−1 are due to the C–H stretching modes −1 of CH2 and CH3. In addition, the absorption band at 1714 cm was ascribed to C=O stretching vibration. At 1608 cm−1, a vibration band was assigned to the deformation of C=C originated from an alkene group, also present in the molecular structure of this compound. In the same spectrum, other typical bands of OMC were observed at 1466 cm−1 assigned to C=C group characteristics of the aromatic ring; at 1258 cm−1, asymmetric deformation of C–O–C, and at 984 cm−1, assigned to vibrations bands of C–H bond characteristics of the aromatic ring [11] (Figure9a). FTIR spectra of SC/GA displayed a Polymers 2021, 13, x FOR PEER REVIEW 12 of 18

470 °C, the temperature range where GA or SA degradation occurs, corresponding to 60% of weight loss. The third weight loss was due to the carbonization process, with 10% of Polymers 2021, 13, 866 12 of 17 weight loss. The thermal degradation process of the OMC microcapsule presented four thermal events. The first was in the range from 25 to 150 °C, with 15% mass loss due to evaporation of water. In the second event (220–300 °C), there was a significant mass loss, aboutstrong 70%, peak indicating at 3420 the cm −release1, which of the was core due material. to the O–H In the and third stretching event (320–420 vibration, °C), andthere no wasobvious a mass bands loss of appeared about 10%, at 2962 which and was 1714 du cme −to1 ,the respectively decomposition [11] (Figure of GA/SC,9b). However,and the GA/SCthe strong used peaksas wall at materials 3420, 2962, may and have 1714 caused cm−1 were this observedhigh weight in theloss FTIR [33]. spectra The fourth of the weightOMC loss microcapsule, was due to indicating the carbonization that OMC process, was successfully with 8% entrappedof weight byloss. SC/GA The results as wall showedmaterial that and the no OMC interaction thermal occurred stability betweenwas significantly OMC and improved wall material by the (Figure encapsulation9c). This processresult was[34]. in This accordance increased with thermal previous stability results can showing be due that to OMC the thermal were bound resistance to SC/GA of GA/SAvia H-bonding used as a [microcapsule13]. casing, resulting in a slower release.

OMC 100 GA/SC The OMC microcapsule 80

60 Mass (%) Mass 40

20

0 0 100 200 300 400 500 600 700 Temperature (°C) Polymers 2021, 13, x FOR PEER REVIEW 13 of 18

FigureFigure 8. 8.ThermalThermal behavior behavior of ofOMC, OMC, SC/G SC/GA,A, and and the the OMC OMC microcapsule. microcapsule.

FTIR was applied to estimate the interactions of the OMC and SC/GA using OMC and SC/GA as control. FTIR spectra of OMC, GA/SC, and the OMC microcapsules are shown in Figure 9 in the range of 4000–500 cm−1. The spectra of all samples, except for free OMC, showed a stretching band at 3420 cm−1 corresponding to –OH groups [9]. For OMC, the strong peaks around 2962 and 2872 cm−1 are due to the C–H stretching modes of CH2 and CH3. In addition, the absorption band at 1714 cm−1 was ascribed to C=O stretching vibration. At 1608 cm−1, a vibration band was assigned to the deformation of C=C origi- nated from an alkene group, also present in the molecular structure of this compound. In the same spectrum, other typical bands of OMC were observed at 1466 cm−1 assigned to C=C group characteristics of the aromatic ring; at 1258 cm−1, asymmetric deformation of C–O–C, and at 984 cm−1, assigned to vibrations bands of C–H bond characteristics of the aromatic ring [11] (Figure 9a). FTIR spectra of SC/GA displayed a strong peak at 3420 cm−1, which was due to the O–H and stretching vibration, and no obvious bands appeared at 2962 and 1714 cm−1, respectively [11] (Figure 9b). However, the strong peaks at 3420, 2962, and 1714 cm−1 were observed in the FTIR spectra of the OMC microcapsule, indicating

thatFigure OMC 9. Fourierwas successfully transform infraredentrapped (FTIR) by spectraSC/GA ofas OMC wall (materiala), OMC microcapsulesand no interaction (b), and oc- the curredFigure between 9. Fourier OMC transform and wallinfrared material (FTIR) (Figurespectra of9c). OMC This (a ),result OMC wasmicrocapsules in accordance (b), and with the SC/GASC/GA ((cc).). previous results showing that OMC were bound to SC/GA via H-bonding [13]. 3.4. Release Behavior of the OMC Microcapsules 3.4. Release Behavior of the OMC Microcapsules The release property of OMC was a key factor for the idea sunscreen-loaded micro- The release property of OMC was a key factor for the idea sunscreen-loaded micro- capsule. As shown in Figure 10, prepared under optimal conditions, free OMC showed acapsule. fast release As shown rate at in the Figure beginning 10, prepared and then under tended optimal toequilibrium. conditions, free After OMC 12 showed h, OMC a microcapsulesfast release rate released at the beginning about 40% and of then OMC, tended while to freeequilibrium. OMC released After 12 more h, OMC than micro- 65%. Thecapsules release released rate of OMCabout was40% aboutof OMC, 30% while higher free than OMC that released of the OMC more microcapsule. than 65%. The The re- phenomenonlease rate of OMC could was be explained about 30% as: higher (1) the than microcapsules that of the couldOMC protectmicrocapsule. the OMC The from phe- fastnomenon release, could and (2) be SC/GAexplained have as: good (1) the film-forming microcapsules properties, could protect which madethe OMC OMC-loaded from fast microcapsulesrelease, and (2) dense SC/GA with have the good smooth film-forming surface and properties, could not which dissolve made in aqueous OMC-loaded solution mi-

aftercrocapsules curing, leadingdense with to effectively the smooth inhibit surface the releaseand could of OMC. not dissolve These results in aqueous show thatsolution the after curing, leading to effectively inhibit the release of OMC. These results show that the OMC-loaded microcapsule could effectively control the release of OMC, implying that strong interactions may exist between OMC and GA/SC [7,23].

80 The OMC microcapsule 70 OMC

60

50

40

30

20 Cumulative Release (%) Release Cumulative

10

0 024681012 t (h) Figure 10. Cumulative release of OMC and the OMC microcapsule.

In order to deeply reveal the release mechanism of OMC microcapsules, various mathematical models, such as zero-order kinetics model, first-order kinetics model, Hi- guchi model, and Korsmeyer-Peppas model, were applied to fit the experimental data, using the free OMC as control [23]. As shown in Table 5, the release behavior of the OMC microcapsule conformed to the Rigter-Peppas model because of the higher R2 values

Polymers 2021, 13, x FOR PEER REVIEW 13 of 18

Figure 9. Fourier transform infrared (FTIR) spectra of OMC (a), OMC microcapsules (b), and the SC/GA (c).

3.4. Release Behavior of the OMC Microcapsules The release property of OMC was a key factor for the idea sunscreen-loaded micro- capsule. As shown in Figure 10, prepared under optimal conditions, free OMC showed a fast release rate at the beginning and then tended to equilibrium. After 12 h, OMC micro- capsules released about 40% of OMC, while free OMC released more than 65%. The re- lease rate of OMC was about 30% higher than that of the OMC microcapsule. The phe- nomenon could be explained as: (1) the microcapsules could protect the OMC from fast Polymers 2021, 13, 866 release, and (2) SC/GA have good film-forming properties, which made OMC-loaded13 of mi- 17 crocapsules dense with the smooth surface and could not dissolve in aqueous solution after curing, leading to effectively inhibit the release of OMC. These results show that the OMC-loadedOMC-loaded microcapsule microcapsule couldcould effectively effectively control control the the release release of of OMC, OMC, implying implying that that strongstrong interactions interactions may may exist exist between between OMC OMC and and GA/SC GA/SC [[7,23].7,23].

80 The OMC microcapsule 70 OMC

60

50

40

30

20 Cumulative Release (%) Release Cumulative

10

0 024681012 t (h) Figure 10. Cumulative release of OMC and the OMC microcapsule. Figure 10. Cumulative release of OMC and the OMC microcapsule.

InIn order order to to deeply deeply reveal reveal the the release release mechanism mechanism of of OMC OMC microcapsules, microcapsules, various various mathematicalmathematical models, models, such such as zero-orderas zero-order kinetics kinetics model, model, first-order first-order kinetics kinetics model, model, Higuchi Hi- model,guchi model, and Korsmeyer-Peppas and Korsmeyer-Pe model,ppas model, were applied were applied to fit the to experimentalfit the experimental data, using data, theusing free the OMC free asOMC control as control [23]. [23]. As shown As shown in Table in Table5, the 5, the release release behavior behavior of theof the OMC OMC microcapsulemicrocapsule conformed conformed to theto the Rigter-Peppas Rigter-Peppas model model because because of the of higher the higherR2 values R2 (0.99).values For the Rigter-Peppas model, n gave an indication of the release mechanism [35]. The n values in the Rigter-Peppas equation were in the range of 0.43 and 0.85 (Table5), implying that the diffusion and relaxation rates were the dominant mass transfer mechanism. Thus,

the release of OMC from the spherical-shaped microcapsules is driven by a non-Fickian diffusion or anomalous diffusion release phenomenon [30].

Table 5. Kinetic models for the OMC microcapsule release.

Models Parameters OMC The OMC Microcapsule Zero-order k 0.05385 k 0.02945 R2 0.5705 R2 0.8034 k 0.003610 k 0.00277 First-order R2 0.9705 R2 0.9771 k 0.6877 k 0.5318 Higuchi R2 0.8409 R2 0.8041 k 0.6712 k 0.7924 Rigter-Peppas n 0.4571 n 0.5472 R2 0.9812 R2 0.9964

3.5. UV Absorption Effect of the OMC Microcapsules A good sunscreen formulation is very important, which not only depends on the physicochemical properties of the filters, but also on the OMC microcapsule’s delivering capacity [35]. In this study, the sunscreen effect of the OMC microcapsule was studied by using a UV spectrophotometer. As shown in Figure 11, the free OMC and SC had an obvious absorption peak between 280 and 320 nm, but the OMC microcapsule also had the same absorbance in the range of 320–400 nm, indicating that the microcapsule consisted of SC and OMC [36]. The maximum absorbance of the OMC microcapsule was larger than that of the free OMC, implying that the sunscreen effect of the OMC microcapsule might Polymers 2021, 13, x FOR PEER REVIEW 14 of 18

(0.99). For the Rigter-Peppas model, n gave an indication of the release mechanism [35]. The n values in the Rigter-Peppas equation were in the range of 0.43 and 0.85 (Table 5), implying that the diffusion and relaxation rates were the dominant mass transfer mecha- nism. Thus, the release of OMC from the spherical-shaped microcapsules is driven by a non-Fickian diffusion or anomalous diffusion release phenomenon [30].

Table 5. Kinetic models for the OMC microcapsule release.

Models Parameters OMC The OMC Microcapsule k 0.05385 k 0.02945 Zero-order R2 0.5705 R2 0.8034 k 0.003610 k 0.00277 First-order R2 0.9705 R2 0.9771 k 0.6877 k 0.5318 Higuchi R2 0.8409 R2 0.8041 k 0.6712 k 0.7924 Rigter-Peppas n 0.4571 n 0.5472 R2 0.9812 R2 0.9964

3.5. UV Absorption Effect of the OMC Microcapsules A good sunscreen formulation is very important, which not only depends on the physicochemical properties of the filters, but also on the OMC microcapsule’s delivering capacity [35]. In this study, the sunscreen effect of the OMC microcapsule was studied by using a UV spectrophotometer. As shown in Figure 11, the free OMC and SC had an ob- vious absorption peak between 280 and 320 nm, but the OMC microcapsule also had the Polymers 2021, 13, 866 same absorbance in the range of 320–400 nm, indicating that the microcapsule consisted14 of 17 of SC and OMC [36]. The maximum absorbance of the OMC microcapsule was larger than that of the free OMC, implying that the sunscreen effect of the OMC microcapsule might be better than that of free OMC (Figure 11). It was attributed that the OMC microcapsule hadbe betterthe UV than absorption that of freefunction OMC of (Figure chemical 11). su Itnscreen, was attributed and also that had the the OMC effect microcapsule of physical sunscreenhad the UV on absorptionultraviolet functionreflection. of In chemical detail, the sunscreen, OMC encapsulated and also had by the the effect microcapsule of physical stillsunscreen had a good on ultraviolet effect of sunscreen, reflection. the In wall detail, material the OMC also encapsulated had the UV absorption, by the microcapsule and the OMCstill hadmicrocapsule a good effect as a ofspherical sunscreen, particle the wallwith materialmicro-size also had had different the UV degrees absorption, of scat- and teringthe OMC and refraction microcapsule to ultraviolet as a spherical rays and particle absorbing with micro-sizeultraviolet hadrays different [5]. The enhanced degrees of sunscreenscattering effect and refraction was due to ultravioletthe synerg raysistic andeffect absorbing of OMC ultravioletand GA/SC rays [15]. [5 ]. The enhanced sunscreen effect was due to the synergistic effect of OMC and GA/SC [15].

1.0 A：OMC 0.8 B：Microcapsule with OMC C：Microcapsule without OMC 0.6 B 0.4 Absorbance

0.2 A C

0.0 250 300 350 Wavelength (nm)

Polymers 2021, 13, x FOR PEER REVIEW 15 of 18 FigureFigure 11. 11. UltravioletUltraviolet absorption absorption effect effect of ofthe the OMC, OMC, OMC OMC microcapsule, microcapsule, and and microcapsule microcapsule with- with- out OMC. out OMC.

3.6.3.6. EffectEffect ofof MicroencapsulationMicroencapsulation onon SPFSPF ofof SunscreenSunscreen TheThe microcapsulesmicrocapsules werewere used used in in sunscreen sunscreen and and the the SPF SPF value value of of sunscreen sunscreen was was deter- de- minedtermined by anbyin an vitro in vitrotest [test37]. The[37]. formulaThe formula of sunscreen of sunscreen adopts adopts the formula the formula recommended recom- inmended the 2015 in editionthe 2015 of edition the safety of technicalthe safety specification technical specification for cosmetics for [ 28cosmetics]. The amount [28]. The of OMCamount in theof OMC recommended in the recommended formula is 3%, formula but the is standard 3%, but the SPF standard value is16.1. SPF Invalue this is study, 16.1. theIn this sunscreen study, performancethe sunscreen was performance compared was with compared the recommended with the recommended formula by adding formula the sameby adding amount the of same the OMCamount microcapsules of the OMC into micr theocapsules sunscreen. into In the the sunscreen. same formula In the system, same theformula SPF valuesystem, of the sunscreen SPF value used of sunscreen with OMC us microcapsulesed with OMC microcapsules was 19 (Figure was 12 19). (Figure 12).

FigureFigure 12.12. ComparisonComparison ofof SPFSPF betweenbetween microencapsulatedmicroencapsulated sunscreensunscreen andandvarious various .sunscreens.

TheThe additionaddition intointo sunscreensunscreen ofof OMCOMC waswas aboutabout 16%,16%, whichwhich improvedimproved thethe sunscreensunscreen performanceperformance byby 18.75%.18.75%. InIn addition,addition, thethe UVUV absorptionabsorption ofof sunscreensunscreen containingcontaining thethe OMCOMC microcapsulesmicrocapsules could be be observed. observed. As As shown shown in inFigure Figure 13, 13 the, theUV UVabsorption absorption effect effect of sun- of sunscreenscreen containing containing OMC OMC microcap microcapsulessules is higher is higher than that than of that sunscreen of sunscreen with OMC with directly OMC added [38]. In addition, this experiment also compared the microencapsulated sunscreen with the SPF value of 25 on the market. It was found that when the mass ratio of OMC microcapsule reached 6%, the SPF value of OMC microcapsule sunscreen was the same as that of sunscreen on the market. It was found that the UV absorption was enhanced only at 280–320 nm. This is consistent with the UV absorption effect of OMC which is a UVB-stage filter. It is proven that the enhancement effect of sunscreen is due to the in- crease of OMC. Through the application of sunscreen microcapsules in sunscreen prod- ucts, it is found that the microencapsulated sunscreen agent can improve the sunscreen efficacy and can compete with the products on the market [39]. At the same SPF value, it can reduce the use of sunscreen, and has the effect of slow-release and reducing skin con- tact [40].

Figure 13. Ultraviolet absorption effect of sunscreen with the OMC microcapsule.

Polymers 2021, 13, x FOR PEER REVIEW 15 of 18

3.6. Effect of Microencapsulation on SPF of Sunscreen The microcapsules were used in sunscreen and the SPF value of sunscreen was de- termined by an in vitro test [37]. The formula of sunscreen adopts the formula recom- mended in the 2015 edition of the safety technical specification for cosmetics [28]. The amount of OMC in the recommended formula is 3%, but the standard SPF value is 16.1. In this study, the sunscreen performance was compared with the recommended formula by adding the same amount of the OMC microcapsules into the sunscreen. In the same formula system, the SPF value of sunscreen used with OMC microcapsules was 19 (Figure 12).

Figure 12. Comparison of SPF between microencapsulated sunscreen and various sunscreens.

The addition into sunscreen of OMC was about 16%, which improved the sunscreen performance by 18.75%. In addition, the UV absorption of sunscreen containing the OMC Polymers 2021, 13, 866 microcapsules could be observed. As shown in Figure 13, the UV absorption effect of sun-15 of 17 screen containing OMC microcapsules is higher than that of sunscreen with OMC directly added [38]. In addition, this experiment also compared the microencapsulated sunscreen with thedirectly SPF value added of [ 3825]. on In the addition, market. this It was experiment found that also when compared the mass the microencapsulatedratio of OMC microcapsulesunscreen reached with the 6%, SPF the value SPF ofvalue 25 on of the OMC market. microcapsule It was found sunscreen that when was the the mass same ratio of as thatOMC of sunscreen microcapsule on the reached market. 6%, It thewas SPF found value that of the OMC UV microcapsule absorption was sunscreen enhanced was the only atsame 280–320 as that nm. of sunscreenThis is consistent on the market. with the It wasUV foundabsorption that the effect UV absorptionof OMC which was enhancedis a UVB-stageonly atfilter. 280–320 It is nm.proven This that is consistentthe enhanc withement the effect UV absorption of sunscreen effect is due of OMC to the which in- is a creaseUVB-stage of OMC. Through filter. It is the proven application that the of enhancement sunscreen microcapsules effect of sunscreen in sunscreen is due to theprod- increase ucts, itof is OMC. found Through that the themicroencapsulat application ofed sunscreen sunscreen microcapsules agent can improve in sunscreen the sunscreen products, it is efficacyfound and thatcan thecompete microencapsulated with the products sunscreen on the agent market can [39]. improve At the the same sunscreen SPF value, efficacy it and can reducecan compete the use withof sunscreen, the products and onhas the the market effect [of39 slow-release]. At the same and SPF reducing value, it skin can reducecon- the tact [40].use of sunscreen, and has the effect of slow-release and reducing skin contact [40].

A：Sunscreen With OMC 5 B：Sunscreen With Microcapsule C：Mixed sunscreen 4 D：Commercial sunscreen D C

3

2 B Absorbance

1 A

0 200 250 300 350 400 Wavelength (nm)

Figure 13. Ultraviolet absorption effect of sunscreen with the OMC microcapsule.

4. Conclusions In this study, the OMC microcapsule was successfully prepared by complex coacerva- tion based on SC and GA. The concentration of wall materials, the ratio of core materials and wall materials, and the amount of emulsifier can affect the shape and particle size of the microcapsules. The optimum preparation conditions of the OMC microcapsules were obtained as follows: wall core ratio 1:1, the curing agent content of 1%, pH = 2.5, 200 rpm, and encapsulation efficiency was 83.3%. The particle size of the capsules ranged from 5 to 16 µm, and the microcapsules were relatively uniform. The results of TG and FTIR indi- cated that OMC was successfully encapsulated by SC/GA. The SEM showed that the OMC microcapsule dispersed in spherical shape with micro-size. The release behaviors indicated that the OMC microcapsule could effectively inhibit OMC release and showed sustained release behavior compared to free OMC. The UV absorption suggested that the sunscreen effect of the OMC microcapsule was better than free OMC due to the ultraviolet absorption of natural polymer (SC) and the reflection of microcapsules’ core-shell. It was found that the sunscreen performance and SPF value of sunscreen containing OMC microcapsules were higher than those of sunscreen with the same amount of OMC. The sunscreen efficiency can be increased by 18.75% under the same SPF value. The sustained-release effect of sunscreen microcapsules can make the sunscreen performance more lasting. The shielding effect of microcapsules can reduce the direct contact between sunscreen and skin. The results indicated that the OMC microcapsules prepared by complex coacervation would have good potential to be used in sunscreen products.

Author Contributions: Conceptualization, C.X. and H.J.; methodology, X.Z.; software, Z.Y.; vali- dation, C.X., X.Z. and Z.Y.; formal analysis, X.Z.; investigation, C.X.; resources, H.J.; data curation, X.Z.; writing—original draft preparation, C.X.; writing—review and editing, Z.Y.; visualization, X.Z.; supervision, Z.Y.; project administration, H.J.; funding acquisition, H.J. All authors have read and agreed to the published version of the manuscript. Polymers 2021, 13, 866 16 of 17

Funding: The authors thank the National Natural Science Foundation of China (2191101377, 21425627), National Natural Science Foundation of China-SINOPEC Joint fund (U1663220), the Science and Technology Plan Projects of Zhongshan (2016B2118) and Science and Technology Plan Projects of Huizhou (2017G0516063) for providing financial support to this project. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable. Data Availability Statement: The data presented in this study are available on request from the corresponding author. Conflicts of Interest: The authors declare no conflict of interest.

References 1. Sabzevari, N.; Qiblawi, S.; Norton, S.A.; Fivenson, D. Sunscreens: UV filters to protect us: Part 1: Changing regulations and choices for optimal sun protection. Int. J. Women’s Dermatol. 2021, 7, 28–44. [CrossRef][PubMed] 2. Bhattacharya, S.; Sherje, A.P. Development of Resveratrol and Green Tea Sunscreen Formulation for Combined Photoprotective and Antioxidant Properties. J. Drug Deliv. Sci. Technol. 2020, 60, 102000. [CrossRef] 3. Guroji, P.; Qayyum, S.; Kim, T.; Janjetovic, Z.; Athar, M.; Slominski, A. 638 Cyp11a1 derived secosteroid, 20(OH)d3 as a novel therapeutic agent for the prevention and treatment of uvb induced skin cancer. J. Investig. Dermatol. 2020, 140, S86. [CrossRef] 4. Horsham, C.; Ford, H.; Hacker, E. Promoting sunscreen use in adolescents playing outdoor sports using UV detection stick-ers. Prev. Med. Rep. 2020, 19, 101166. [CrossRef][PubMed] 5. Daneluti, A.L.M.; Neto, F.M.; Ruscinc, N.; Lopes, I.; Velasco, M.V.R.; Matos, J.D.R.; Baby, A.R.; Kalia, Y.N. Using ordered mesoporous silica SBA-15 to limit cutaneous penetration and transdermal permeation of organic UV filters. Int. J. Pharm. 2019, 570, 118633. [CrossRef][PubMed] 6. He, H.; Li, A.; Li, S.; Tang, J.; Li, L.; Xiong, L. Natural components in sunscreens: Topical formulations with sun protection factor (SPF). Biomed. Pharmacother. 2021, 134, 111161. [CrossRef][PubMed] 7. Slomberg, D.L.; Catalano, R.; Bartolomei, V.; Labille, J. Release and fate of nanoparticulate TiO2 UV filters from sunscreen: Effects of particle coating and formulation type. Environ. Pollut. 2021, 271, 116263. [CrossRef][PubMed] 8. Keyes, E.; Werth, V.P.; Brod, B. Potential allergenicity of commonly sold high SPF broad spectrum sunscreens in the United States; from the perspective of patients with autoimmune skin disease. Int. J. Women’s Dermatol. 2019, 5, 227–232. [CrossRef][PubMed] 9. Volpe, V.; Nascimento, D.S.; Insausti, M.; Grünhut, M. Octyl p-methoxycinnamate loaded microemulsion based on Ocimum basilicum essential oil. Characterization and analytical studies for potential cosmetic applications. Colloids Surf. A Physicochem. Eng. Asp. 2018, 546, 285–292. [CrossRef] 10. Mota, M.D.; da Morte, A.N.; Silva, L.C.R.C.E.; Chinalia, F.A. Sunscreen protection factor enhancement through supple-mentation with Rambutan (Nephelium lappaceum L) ethanolic extract. J. Photochem. Photobiol. B 2020, 205, 111837. [CrossRef] 11. Nataraj, B.; Maharajan, K.; Hemalatha, D.; Rangasamy, B.; Arul, N.; Ramesh, M. Comparative toxicity of UV-filter Octyl meth-oxycinnamate and its photoproducts on zebrafish development. Sci. Total Environ. 2020, 718, 134546. [CrossRef] 12. Cahova, J.; Blahova, J.; Marsalek, P.; Doubkova, V.; Franc, A.; Garajová, M.; Tichy, F.; Mares, J.; Svobodova, Z. The biological activity of the organic UV filter ethylhexyl methoxycinnamate in rainbow trout (Oncorhynchus mykiss). Sci. Total Environ. 2021, 774, 145570. [CrossRef][PubMed] 13. Yamada, M.; Mohammed, Y.; Prow, T.W. Advances and controversies in studying sunscreen delivery and toxicity. Adv. Drug Deliv. Rev. 2020, 153, 72–86. [CrossRef][PubMed] 14. Castro, N.R.; Pinto, C.d.S.C.; de Campos, V.E.B.; Cardoso, V.; Vermelho, A.B.; Santos, E.P.D.; Mansur, C.R.E. Development of hybrid vesicular nanosystems composed of and chitosan for octyl methoxycinnamate encapsulation. Colloid. Surf. A 2021, 608, 125476. [CrossRef] 15. Eriksson, V.; Trojer, M.A.; Vavra, S.; Hulander, M.; Nordstierna, L. Formulation of polyphthalaldehyde microcap-sules for immediate UV-light triggered release. J. Colloid Interface Sci. 2020, 579, 645–653. [CrossRef][PubMed] 16. Budinˇci´c,J.M.; Petrovi´c,L.; Ðeki´c,L.; Fraj, J.; Buˇcko,S.; Katona, J.; Spasojevi´c,L. Study of vitamin E microencapsulation and controlled release from chitosan/sodium lauryl ether sulfate microcapsules. Carbohydr. Polym. 2021, 251, 116988. [CrossRef] [PubMed] 17. Li, C.; Fang, K.; He, W.; Li, K.; Jiang, Y.; Li, J. Evaluation of chitosan-ferulic acid microcapsules for sustained drug delivery: Synthesis, characterizations, and release kinetics in vitro. J. Mol. Struct. 2021, 1227, 129353. [CrossRef] 18. Ferreira, S.; Nicoletti, V.R. Microencapsulation of ginger oil by complex coacervation using atomization: Effects of polymer ratio and wall material concentration. J. Food Eng. 2021, 291, 110214. [CrossRef] 19. Vargas, S.A.; Delgado-Macuil, R.J.; Ruiz-Espinosa, H.; Rojas-López, M.; Amador-Espejo, G.G. High-intensity ultrasound pre- treatment influence on whey isolate and its use on complex coacervation with kappa carrageenan: Evaluation of se-lected functional properties. Ultrason Sonochem. 2021, 70, 105340. [CrossRef][PubMed] 20. González-Monje, P.; García, A.A.; Ruiz-Molina, D.; Roscini, C. Encapsulation and sedimentation of nanomaterials through complex coacervation. J. Colloid Interface Sci. 2021, 589, 500–510. [CrossRef] Polymers 2021, 13, 866 17 of 17

21. Boyd, B.J. Characterisation of drug release from cubosomes using the pressure ultrafiltration method. Int. J. Pharm. 2003, 260, 239–247. [CrossRef] 22. Schwarzl, R.; Du, F.; Haag, R.; Netz, R.R. General method for the quantification of drug loading and release kinetics of nanocarriers. Eur. J. Pharm. Biopharm. 2017, 116, 131–137. [CrossRef][PubMed] 23. Kanha, N.; Regenstein, J.M.; Surawang, S.; Pitchakarn, P.; Laokuldilok, T. Properties and kinetics of the in vitro release of an-thocyanin-rich microcapsules produced through spray and freeze-drying complex coacervated double emulsions. Food Chem. 2021, 340, 127950. [CrossRef][PubMed] 24. Azhdari, E.; Emami, A.; Ferreira, J. Drug release from a surface erosion biodegradable viscoelastic polymeric platform: Analysis and numerical simulation. Comput. Math. Appl. 2020, 80, 3004–3026. [CrossRef] 25. Tomazelli, L.C.; Ramos, M.M.D.A.; Sauce, R.; Cândido, T.M.; Sarruf, F.D.; Pinto, C.A.S.D.O.; de Oliveira, C.A.; Rosado, C.; Velasco, M.V.R.; Baby, A.R. SPF enhancement provided by rutin in a multifunctional sunscreen. Int. J. Pharm. 2018, 552, 401–406. [CrossRef][PubMed] 26. Choi, Y.-R.; Chang, Y.H. Microencapsulation of gallic acid through the complex of whey protein concentrate-pectic polysac-charide extracted from Ulmus davidiana. Food Hydrocoll. 2018, 85, 222–228. [CrossRef] 27. Damiani, E.; Puglia, C. Nanocarriers and Microcarriers for Enhancing the UV Protection of Sunscreens: An Overview. J. Pharm. Sci. 2019, 108, 3769–3780. [CrossRef][PubMed] 28. Romanhole, R.C.; Fava, A.L.M.; Tundisi, L.L.; de Macedo, L.M.; dos Santos, É.M.; Ataide, J.A.; Mazzola, P.G. Unplanned absorption of sunscreen ingredients: Impact of formulation and evaluation methods. Int. J. Pharm. 2020, 591, 120013. [CrossRef] 29. Marques da Silva, T.; Lopes, E.J.; Codevilla, C.F.; Cichoski, A.J.; Flores, É.M.D.M.; Motta, M.H.; da Silva, C.D.B.; Grosso, C.R.F.; de Menezes, C.R. Development and characterization of microcapsules containing Bifidobacterium Bb-12 produced by complex coacervation followed by freeze drying. LWT 2018, 90, 412–417. [CrossRef] 30. Frelichowska, J.; Bolzinger, M.-A.; Pelletier, J.; Valour, J.-P.; Chevalier, Y. Topical delivery of lipophilic drugs from o/w Pick-ering emulsions. Int. J. Pharmaceut. 2009, 371, 56–63. [CrossRef] 31. Da Cruz, M.C.R.; Dagostin, J.L.A.; Perussello, C.A.; Masson, M.L. Assessment of physicochemical characteristics, thermal stability and release profile of ascorbic acid microcapsules obtained by complex coacervation. Food Hydrocoll. 2019, 87, 71–82. [CrossRef] 32. Li, H.; Feng, Y.; Cui, Y.; Ma, Y.; Zheng, Z.; Qian, B.; Wang, H.; Semenov, A.; Shchukin, D. Polyurea/polyaniline hybrid shell mi-crocapsules loaded with isophorone diisocyanate for synergetic self-healing coatings. Prog. Org. Coat. 2020, 145, 105684. [CrossRef] 33. Qian, B.; Zheng, Z.; Liu, C.; Li, M.; D’Sa, R.A.; Li, H.; Graham, M.; Michailidis, M.; Kantserev, P.; Vinokurov, V.; et al. Mi- crocapsules Prepared via Pickering Emulsion Polymerization for Multifunctional Coatings. Prog. Org. Coat. 2020, 147, 105785. [CrossRef] 34. Su, J.-F.; Schlangen, E. Synthesis and physicochemical properties of high compact microcapsules containing rejuvenator ap-plied in asphalt. Chem. Eng. J. 2012, 198–199, 289–300. [CrossRef] 35. Kanha, N.; Surawang, S.; Pitchakarn, P.; Laokuldilok, T. Microencapsulation of copigmented anthocyanins using double emulsion followed by complex coacervation: Preparation, characterization and stability. LWT 2020, 133, 110154. [CrossRef] 36. Andreani, T.; Dias-Ferreira, J.; Fangueiro, J.; Souza, A.; Kiill, C.; Gremião, M.; García, M.; Silva, A.; Souto, E. Formulating octyl methoxycinnamate in hybrid -silica nanoparticles: An innovative approach for UV skin protection. Heliyon 2020, 6, e03831. [CrossRef] 37. Yang, Y.; Ako-Adounvo, A.-M.; Wang, J.; Zhang, J.; Willett, D.; Yilmaz, H.; Korang-Yeboah, M.; Hsu, H.-J.; Coelho, S.G.; Adah, S.A.; et al. In Vitro Testing of Sunscreens for Dermal Absorption: A Platform for Product Selection for Maximal Usage Clinical Trials. J. Investig. Dermatol. 2020, 140, 2487–2495. [CrossRef] 38. Gollavilli, H.; Hegde, A.R.; Managuli, R.S.; Bhaskar, K.V.; Dengale, S.J.; Reddy, M.S.; Kalthur, G.; Mutalik, S. Naringin nano- ethosomal novel sunscreen creams: Development and performance evaluation. Colloids Surf. B Biointerfaces 2020, 193, 111122. [CrossRef] 39. Infante, V.; Campos, P.M.; Calixto, L.; Darvin, M.; Kröger, M.; Schanzer, S.; Lohan, S.; Lademann, J.; Meinke, M. Influence of physical–mechanical properties on SPF in sunscreen formulations on ex vivo and in vivo skin. Int. J. Pharm. 2021, 598, 120262. [CrossRef] 40. Lin, Y.-C.; Fang, Y.-P.; Hung, C.-F.; Yu, H.-P.; Alalaiwe, A.; Wu, Z.-Y.; Fang, J.-Y. Multifunctional TiO2/SBA-15 mesoporous sili-ca hybrids loaded with organic sunscreens for skin application: The role in and pollutant adsorption with reduced sunscreen permeation. Colloids Surf. B 2021, 202, 1111658. [CrossRef][PubMed]