Hydrogels: a Review Shikha Yadav* and Jitender Madan Hygia Institute of Pharmaceutical Education and Research, Lucknow, (U.P.) - India

Review Article ISSN: 0976-7126 CODEN (USA): IJPLCP Yadav & Madan, 11(6):6711-6717, 2020

[[ Hydrogels: A review Shikha Yadav* and Jitender Madan Hygia Institute of Pharmaceutical Education and Research, Lucknow, (U.P.) - India

Abstract Article info Hydrogels are hydrophilic, three dimensional and polymers network that hold the large quantity of water of biological fluids. Water is the large Received: 18/04/2020 constituents of human body which applied for the biomedical purposes. Polymers are playing significance role in the pharmaceutical field. Revised: 08/05/2020 Hydrogels are biomaterials due to their important quantities such as biocompatibility, biodegradability and non toxic properties and these Accepted: 22/06/2020 properties makes hydrogel acceptable for medical and pharmaceutical field. This article concerning the general knowledge about hydrogels i.e. © IJPLS significance, method of preparation, synthesis of hydrogels, chemical and physical properties, feature, advantage and disadvantage.

www.ijplsjournal.com Keyword: Hydrogel, Feature, Classification, Application.

Introduction examples of the transdermal formulations [4]. Hydrogels are hydrophilic, three dimensional Hydrogel have different method for the in vivo network that hold the large quantity fluid water is administration of drug, which are based on the the large constituents of human body which localization and pathological condition. Most applied for the biomedical purposes. Generally it available topical subcutaneous, orthotopic, based on the chemical composition which is intraperitoneal, oral, ocular and rectal. Topical or responsive to the various stimuli such as heating, transdermal plays a vital role for the skin pH, light, and chemicals [1]. Hydrogels can also infection, subcutaneous for toxicological effect, be prospect by rheological manners and swollen orthotopic and intraperitoneal injections for polymer network which flatter hydrated in the therapy while oral administration have some liquid media that are referred to as the hydrogel disadvantage due to the presence of some structure [2]. Many theories are involved in the digestive enzymes [5]. According to Witchterls swelling mechanism such as Equilibrium swelling and Lim in 1960, cross-linked hydroxyl ethyl theory, Rubber elastic theory, Mechanism of methaacrylate has excellent water holding Gelation and Calculation of mesh size. Hydrogels capacity, high water retention, good can be prepared from natural polymers are biocompatibility and biodegradability, limited or polysaccharides, polypeptide [1, 3]. Hydrogels minimal toxicity and simplified synthetic method. formulation applied on the skin surfaces which Hydrogels are formed by physical and chemical categories into two groups such as topical and cross- linking network. Conductive hydrogel, transdermal route. Topical formulations provide Injective hydrogel, Double network hydrogel, the drug at the particular site of the skin surfaces Responsive hydrogel, Nanocomposite hydrogel, without systemic exhibition while transdermal sliding hydrogel and other Novel hydrogel [6]. formulations applied to the local area of the skin surfaces which maintain and deliver the effective *Corresponding Author concentration of drug in the systemic circulations. E.mail: [email protected] Aerosol, spray, semi solid and patches are the

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. Drug should have adapted hydrophilicity and molecular weight of less than 500 Daltons. . PH value of drug between 5 and 9. . Drug must be high acidic or alkaline in solution which are not suitable for topical drug delivery system. Advantage and disadvantage of hydrogel [11, 12] Advantage Disadvantage

Hydrogels are Limitation of hydrogels Fig. 1: Hydrogel Network [6] homogeneous to the in contact lenses is natural tissue due to hypoxia, dehydration, high water holding lenses deposition and capacity and it contain red eye reactions. the degree of flexibility. It should be It should be non biodegradable, adherent, hard to biocompatible and good sterilized and hard to transport properties. load with drugs or nutrients. It may be low toxicity High cost Hydrogels can be It has low mechanical injected and easily to strength. Fig. 2: Structure of hydrogel [7] modify. Advanced hydrogel materials have unique It have capability to It can be hard to properties to swell under particular sympathetic change of pH, handle. circumstances and response to available of stimuli temperature and that are referred to as the environmental or stimuli concentration. sensitive. Some synthetic polymer hydrogels are included cross- linking hydrogel, water in Classification of hydrogel [13, 14, 15] hydrogel, poly (vinyl alcohol), poly (hydroxyethyl  Classification based on source methaacrylate), polyvinyl pyrrolidone,  Hydrogel can be divided into two group i.e. polymidine, polyacrylate, polyurethane, Natural origin and synthetic origin. polyethylene glycol and derivatives [8]  Classification based on the polymeric composition/ Method of preparation Feature of hydrogel [9, 10]  Homopolymeric hydrogels- It is known as the . It should have rewetting capacity and polymeric network which acquire from a single highest absorbancy under load (AUC). species of the monomer. These hydrogels have . They exhibit little residual manners and cross linked skeletal structure which depend on soluble content. the nature of the polymerization technique and . During storage condition it has good monomers. stability and durability in the swelling  Copolymeric hydrogels- Copolymeric hydrogels environment. are referred to as different monomers unit in . It is colorless, odorless, non toxic and also which included one hydrophilic component. exhibit highest photo stability in nature.  Multipolymer Interpenetrating polymeric . Hydrogel must be pH neutrality after in hydrogels (IPN) - It is two independent natural swelling media and highest polymer or synthetic polymers component. In this biodegradability. type of classification one polymer is noncross linked polymer network.

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Classification based on the configuration/ physical structure of the network According to the physical structure and chemical composition, these hydrogels can be classified into Amorphous (non- crystalline), semi crystalline, hydrogen bonded, super molecular structure or hydro colloidal aggregation. Classifications based on the physical appearance Hydrogels are film, matrix and microsphere which depend on the polymerization techniques. Classifications based on the type of the cross linking Hydrogels are divided into two categories i.e. physical and chemical nature of the cross linking. Physical linking is the transient junction while chemical linking is the permanent junctions in whom both junctions are ionic interactions, hydrogen bonds, or hydrophobic interaction.

Classifications based on the network electrical charges/ ionic charges Synthesis of hydrogel On the basis of presence or absence of electrical Physical cross linking [18] charges hydrogels are divided into four categories Physical or reversible gels have stable by i.e. Ionic (anionic or cationic), Non ionic proportionately weak interaction established (neutral), amphoteric electrolytes (ampholytic), polymers chain such as hydrogen bond, ionic zwitterionic. interaction or hydrophobic. It incorporated Based on the mechanical controlling the drug cooling or heating polymers solution, ionic release interaction, hydrogel bonding, freeze thaw cycles, It involves the diffusion controlled, swelling maturation or aggregation controlled, chemically controlled, and Chemical method [18] environmentally responsive release system, These processes are synthesis of hydrogels diffusion controlled, chemically controlled, incorpoted the chemical cross linking, grafting of environment responsive system. monomers. Chemical cross linking are established Preparation method of hydrogel [16] the bonds in the middle of polymer chain. Cross Hydrogels can be prepared from the different linking of natural and synthetic polymers contain method i.e. cold method, fusion method and hydroxyl, carboxylic and amine groups and dispersion method. grafting process included the polymerization of Dispersion method is widely used for the monomer preparation of gel. In these process polymers was Use of gelling agent [19] dispersed in distilled water with constant stirring Some substances with their suitable concentration and heat the colloidal viscous dispersion get clear (wt %) are used for the gelling agent such as gel solution. Drugs were dissolving in solvent collagen (0.2- 0.4), gelatin (2-15), agar (0.1-1), media and added to the dispersion. Using TEA alginate (0.5-1), gellum gum (0.5-1), pectins (0.8- (Triethanolamine) until it reaches desired pH 2), starch (6), carboxymethylecellulose (4-6), value ex. methylcellulose gels are prepare from hydroxypropylmethylcellulose (2-10), dispersion method than in cold water. Fusion hydroxypropylcellulose (8-10), methylcellulose method are depends on the gelling agent such (2-4), Polaxomer (15-50), carbomer (0.5-2) etc. tragacanth gels are prepared at low temperature Isostatic ulta high pressure (IUHP) [20] and Carbopol gels have unique procedure. Cold Some natural biopolymers like starch are come in method is used for the heat labile drugs. contact with IUHP of 300-700 MPa for 5 or 20

International Journal of Pharmacy & Life Sciences Volume 11 Issue 6: June. 2020 6713 Review Article ISSN: 0976-7126 CODEN (USA): IJPLCP Yadav & Madan, 11(6):6711-6717, 2020 minutes, which accompany the changes in the biomedical applications are ligament, wound morphological structure of the polymers (i.e. dressing, tendon repairs, and matrix for drug formation of the gelatinization of the starch delivery, tissue engineering, and cartilage molecules). Temprature of Isostatic ulta high replacement materials. pressure are varies from 40-52°C. Cross linking: - It is the important properties of Nucleophilic substitution reaction [20] the hydrogel. Physical cross linking and chemical N-2-dimethylamino ethylmethacrylamine bound gel are the category of cross linking (DMAEMA) is pH and temperature sensitive hydrogels. Many collaborative reactions are hydrogels. Nucleophilic substitution reaction involve for the cross linking process such as occurs between chloride and 2- diemethilamino Michael’s reaction, Michaelis-Arbuzov reaction, ethylamine. and nucleophilic addition reactions. Natural and synthetic polymers [21] Biocompatible properties: - Hydrogels are the Natural polymers and their derivatives are of non toxic and biocompatibity in behavior. Most many types such as Cationic polymers (plylysine, polymers used for cytotoxity and in vitro toxic chitosane), Anionic polymers (pectin and alginic test. Biocompatibity consist of two polymer i.e. acid), and Neutral polymers (agrose) and biosafty and Biofunctionality. Amphoteric polymers (gelatin and fibrin). Porosity and permeation:- Pores size could be Synthetic polymers are polyesters which included created in hydrogel by the phase separation PEG-PLA-PEG, PEG-PLGA-PEG while process and it depends on the three factor i.e. combination of both natural as well as synthetic concentration of the chemical cross- links of the polymers is P (PEG-CO-Peptides), Alginate-g polymer strand, net charge of polyelectrolytes and (PEO-PPO-PEO). concentration of the physical entanglement of the Semi interpenetrating network and inter polymer strands . penetrating network [22] Drug release mechanism from hyrdogel devices Semi interpenetrating the linear polymers, it [20, 25, 26] penetrate cross linked network without involving Many factor affected in drug delivery mechanism the chemical bond between them while such as arrangement of hydrogel (type of polymer, interpenetrating network are inter connected of drug and additives), configurations (shape and two molecules which synthesized other and by size), preparation method, environmental this process dense hydrogels are formed. circumstances, physical and chemical phenomena. Sophisticated and simple models are depending on Significance of hydrogel [23, 24] the rate limiting steps for controlled release which Physical and chemical properties: - Hydrogel are divided into the following ways i.e. depend on the two major effect i.e. particles size Diffusion controlled model follow the flick’s law and molecules attraction or repulsion. It is of diffusion which play an effective for drug realistic design to know the solute molecules release from hydrogels. Controlled release drug interact with the gel particularly they partition diffusivities are calculated from the volume, between the gel phase and liquid phase. hydrodynamics or obstruction based theories. Swelling: - Hydrogel is the hydrophilic, cross Types of diffusion are divided into reservoir linked (physically or chemically) polymer chain system and polymer hydrogel membrane. are able to absorb the large quantity of the water Swelling controlled release is slower than the holding capacity. Generally dry hydrogel start to diffusion controlled model. Mechanism of this soak water range from 10-20%. Temprature, pH, model includes moving boundary conditions. ionic species, and electric signal can be changes Examples are drug with HPMC, combination of the appearance of hydrogel and this variation may methyl/ cellulose with HPMC, Methacel matrices. take place at microscope level. Chemical controlled release model are Mechanical properties: - Mechanical properties determined by the reaction take place within drug can be depending on the nature of the material. It matrix. Cleavage of polymer chain i.e. enzymatic required a gel with stiffness by increasing the degradation or hydrolytic or reversible or cross linking chain. The evaluation parameters of irreversible reaction take place between the

International Journal of Pharmacy & Life Sciences Volume 11 Issue 6: June. 2020 6714 Review Article ISSN: 0976-7126 CODEN (USA): IJPLCP Yadav & Madan, 11(6):6711-6717, 2020 polymer chain and releasable drug are example of are >80um and combined with polymer or the chemically control release. ceramics. It is responsible for the cell migration Biomedical application of hydrogel into the core of scaffold, angiogenesis and Drug delivery [27, 28, 29] provides of supplements to the cell. Sterilization If drug conduct hydrogel, brought near the liquid of hydrogel is an alter characteristics of scaffold. media then water make a holes into the apparatus or arrangement and dismiss the drug into the solution. According to the Brownian motion diffusion play a vital role for the dissolution of drug into a liquid media. Hydrogels are important for the enlargement the control drug delivery system for a long duration and these system can be categories into two system i.e. reservoir system and matrix system.

(drug diffusion from the core through the hydrogel membrane) Fig. 4: Reservoir system

Fig. 6: Multidisciplinary approach of tissue engineering Wound dressing [30] Hydrogels have capability of stimulation the regeneration of skin. It can be loaded with drug which is responsible for the treatment of wound.

Fig. 5: Matrix system Various model and equations are useful for the mechanism of drug release such as Zero order kinetics, First order kinetic, Baker- Lonsdale model, Kerseymeres peppas model and Fig.7: Diagram of wound dressing Hopfenberg model. Environment and Bacterial culture [31] Oral, topical, transdermal, vaginal, ophthalmic, Matrix have the capability to hold the purifying intranasal, rectal, injectable, micro/ nanogel the microorganism. Chlorella and spirulina these delivery vehicles, hydrogel mediated drug microorganisms are used to remove the pollutants delivery vehicles are the different administration chemical from water resources. While in bacterial of drug delivery system. culture agar is very popular substrate in The anatomy and physiological applications for application of biotechnology. Various type of agar stabilized drug delivery system [15] like Columbi agar, Brucella agar, Schaedler agar Tissue engineering [30] or Trypicasesoy agar are gives a suitable Tissue engineering (TE) play an important role in environment for their culture on a solid. the regenerative medicine. It is categories into Hydrogel to fix bone replacement [32] three part i.e. cell/ tissue, scaffold and During the replacement of heep and knee are implantation and or grafting. Pore size of scaffold laminar with hydrogel which swell or enlarge in

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Cite this article as: Yadav S. and Madan J. (2020). Hydrogels: A Review, Int. J. of Pharm. & Life Sci., 11(6): 6711- 6717. Source of Support: Nil Conflict of Interest: Not declared For reprints contact: [email protected]

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