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Effect of Zeta Potential on the Properties of Nano-Drug Delivery Systems - a Review (Part 2)

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Effect of Zeta Potential on the Properties of Nano-Drug Delivery Systems - a Review (Part 2) Honary & Zahir 2b Tropical Journal of Pharmaceutical Research April 2013; 12 (2): 265-273 ISSN: 1596-5996 (print); 1596-9827 (electronic) © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights reserved. Available online at http://www.tjpr.org http://dx.doi.org/10.4314/tjpr.v12i2.20 Review Article Effect of Zeta Potential on the Properties of Nano-Drug Delivery Systems - A Review (Part 2) Soheyla Honary* and Foruhe Zahir Mazandaran University of Medical Sciences, School of Pharmacy, Sari, Iran *For correspondence: E-mail: [email protected]; [email protected] Received: 18 August 2012 Revised accepted: 7 January 2013 Abstract The zeta potential (ZP) of colloidal systems and nano-medicines, as well as their particle size exert a major effect on the various properties of nano-drug delivery systems. Not only the stability of dosage forms and their release rate are affected but also their circulation in the blood stream and absorption into body membranes are dramatically altered by ZP. In this paper the effect of ZP on the various properties of nano-medicines are reviewed. Furthermore, the ability of employing zeta potential to target drug delivery systems to, and drug release at specific sites of the body are discussed. Keywords: Nano-medicines, Zeta potential, Drug targeting, Site-specific release, Dosage form stability Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), Scopus, International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index Copernicus, EBSCO, African Index Medicus, JournalSeek, Journal Citation Reports/Science Edition, Directory of Open Access Journals (DOAJ), African Journal Online, Bioline International, Open-J-Gate and Pharmacy Abstracts INTRODUCTION Because many proteins, DNA and cell membrane surface are slightly anionic, so a Nanoparticle surface is a very important positive ZP not only has benefits for enhanced consideration in targeting drug delivery. DNA loading efficiency also might provide the Conventional nanoparticles (without surface effective accumulation in the target cells [4]. modification) and negatively charged particles “Complexes” is the term in which particle can be rapidly opsonized and massively cleared formation is elicited by the tropism between DNA by fixed macrophages of the reticuloendothelial molecules and nanoparticles with positive system (RES) in the blood stream. Surface surface charge [5]. modification of nano-drug delivery systems is the most common strategy to controlling the The particle size and ζ-potential of vector/pDNA opsonization process and thus sustain the particles can influence the intracellular trafficking systems for longer period in the blood stream. of particles and subsequent transfection Suitable ZP can improve drug release profiles at efficiency. The particles are large at N/P ratios of specific sites as well as their stability in dosage 2:1 to 4:1, corresponding to neutral or slightly forms. positive zeta potentials, which demonstrates that particles possibly be gathered into a mass at the Effect of ZP on gene delivery systems The neutral condition. The ZP of binary complexes transfection efficiency of gene vector depends on increases with increase in N/P ratios, and neutral the particle size and zeta potential [1]. A system or positive ZP were observed for N/P ratios of 2 that is simply negatively charged [2] or with a and greater. The transfection efficiency of gene positive surface charge density might be vector depends on the particle size and zeta desirable for loading DNA molecules [3]. potential. Moreover, excess positive charge on Trop J Pharm Res, April 2013;12 (2): 265 Honary & Zahir 2b the complexes can cause the nonspecific binding Cationic nanoparticles combine the advantages and uptake by non targeted cells. Thus for of nanoparticles as a drug carrier and complexes with targeting ligand, a weekly complexation ability with nucleic acid in acting as positively charged surface is preferable for the the gene carrier. With better biocompatibility and specific binding by receptor-mediated easy producing property, cationic nanoparticles endocytosis. When complexes of N/P higher than have gained more and more attention in the gene the optimal value were added to the cultured delivery area. Unlike the delivery of plasmid cells, specific binding was inhibited in the DNA, transport of dsRNA is much easier since presence of excess peptides. According to there is no need to deliver dsRNA into the cell literature, arginine-rich peptides also show the nucleus (fig 1). Previous polymeric nanoparticles same trend [6]. mediated gene delivery method tend to use double emulsion technique loading the Previous studies aimed to develop an amphoteric therapeutic gene and was limited by the low hyaluronic acid (HA) derivative with encapsulation efficiency of the drug. Moreover, polyethyleneimine (PEI) chains (HAP) for gene during the process of preparing nanoparticles delivery to overcome the disadvantages of PEI through double emulsion technique, the contact as gene carrier including the cytotoxicity caused of the dsRNA with a lot of organic solvent and by excess of positive charge, non-special the involvement of sonication procedure might interaction and aggregation in the blood, and damage or denature the dsRNA. non-target gene delivery. At charge ratio of 1, where the complex could not form completely, Now, more and more researchers have the zeta potential was negative. But an employed cationic nanoparticles simply because interesting result was observed in that the zeta it is an easy, safe and efficient way to carry potential of HAP/DNA complex with higher therapeutic substances. Chitosan and molecular weight HA at certain charge ratio was polyethyleneimine (PEI) have both been used as positive, but not negative charge as expected. cationic coating agents. The results demonstrate Moreover, electrochemical equilibrium process that PEI 25 kDa is slightly better than the was observed in the course of determining ZP, chitosan by showing higher gene transfection which signified that the condensation process of efficiency and higher loading efficiency of RNA. DNA by HAP might be complicate [7]. These results revealed that two factors affect the siRNA delivery efficacy of cationic nanoparticles Cationic nanoparticles of biodegradable in terms of higher DNA loading capacity than polymers such as poly (lactide) (PLA) have been chitosan [10]. In addition, the zeta potentials of shown to be promising carrier systems for DNA poly-siRNA/PEI complexes (1.54 ± 0.72 mV) and siRNA delivery. The cationic poly (d,l-lactide- were lower than that of mono-siRNA/PEI co-glycolide) (PLGA)–PEI, PLGA–chitosan and complexes (22.39 ± 0.53 mV), implying that most methoxy poly (ethylene glycol)–poly (lactide) of the positively charged PEI chains in poly- PLGA/PEI and mPEG–PLA/PEI nanoparticles siRNA/PEI complexes were closely covered with were prepared by a nanoprecipitation method. the strongly anionic poly-siRNA. The most Surface modification of the nanoparticles into positively charged portion of PEI in mono- cationic surface was done to facilitate the loading siRNA/PEI complexes protruded from the of negatively charged dsRNA. The results complexes due to the weak electrostatic showed that zeta potential of the nanoparticles interaction with lower anionic charged mono- significantly changed from negative to positive siRNA. These results clearly reveal that poly- value after being modified by the siRNA produced more nano-sized and compact polyethyleneimine (PEI) 25 kDa and chitosan. complexes than mono-siRNA via electrostatic Since the surface charge of the nanoparticle interactions with PEI [11]. delivery system was primarily determined by the amount of the amine group (NH2+) of PEI 25 A good complexation of the negatively charged kDa and the chitosan coated on the surface of siRNA to the cationic dex-HEMA-co-TMAEMA the nanoparticles, four groups of nanoparticles nanogels is a prerequisite to successfully deliver demonstrated different zeta potential indicating siRNA across plasma membrane into cytosol. To different charge potential of the nanoparticles. All evaluate this, nanogel samples were titrated with of the four nanoparticles showed great dsRNA siRNA and the resultant zeta-potential of the loading potential. This further confirmed the siRNA-loaded nanogels was measured. Clearly, previous results that nanoparticles through the loading of the nanogels with siRNA is polycations modification can absorb the negative reflected in the zeta-potential value as can be charge nucleic acid and load it efficiently [8] and seen in the typical sigmoidal curves that are the charge interaction is firm enough to absorb obtained; the lower positive surface charge of the the dsRNA at the surface of nanoparticles [9]. DS 8.9 nanogels may result in a less efficient Trop J Pharm Res, April 2013;12 (2): 266 Honary & Zahir 2b cellular internalization. Fewer uptakes of DS 8.9 conditions [14]. The membrane of red blood cells nanogels by Huh-7 cells could indeed be (RBC) is also soft and composed of two-sub confirmed by flow cytometry and is therefore one layers, the outer sub layer being negatively of the reasons which explain the lower gene charged and the inner one being positively silencing by DS 8.9 nanogels [12]. charged. According to some studies, the dominant factor to control the interaction between RBC and the synthetic polymer is the softness of the nanoparticle surface. It is considered
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