phkineticaФармакокинетика и ФармакодинамикаPharmacokinetics and Pharmacodynamics2587-78362686-8830ООО «Издательство ОКИ»phkinetica-155Research ArticleАКТУАЛЬНЫЙ ОБЗОРCURRENT REVIEWSВлияние высокомолекулярных вспомогательных веществ на оптимизацию фармакокинетических свойств лекарственных препаратовEffects of the high-molecular excipients on optimization of the pharmacokinetic properties of drugsБочковП. О.BochkovP. .noemail@neicon.ruКолывановГ. Б.KolyvanovG. .noemail@neicon.ruЛитвинА. А.LitvinA. .noemail@neicon.ruЖердевВладимир ПавловичZherdevV. .zherdevpharm@mail.ruШевченкоР. В.ShevchenkoR. .noemail@neicon.ruФГБНУ «НИИ фармакологии имени В.В. Закусова»РоссияFSBSI «Zakusov Institute of Pharmacology»Russian Federation20160904202001311Copyright © Бочков П.О., Колыванов Г.Б., Литвин А.А., Жердев В.П., Шевченко Р.В., 20202020Бочков П.О., Колыванов Г.Б., Литвин А.А., Жердев В.П., Шевченко Р.В.Bochkov P..., Kolyvanov G..., Litvin A..., Zherdev V..., Shevchenko R...Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmacokinetica.ru/jour/article/view/155

В обзоре рассмотрено использование различных природных и синтетических вспомогательных веществ, как в оптимизации свойств лекарственных форм, так и при изготовлении различных систем доставки лекарственных препаратов. Приведена краткая характеристика вспомогательных веществ с точки зрения их влияния на физико-химические характеристики лекарственных форм.

Applying of different natural and synthetic excipients as in developing of drug forms as manufacturing various drug delivery systems was shown.

вспомогательные веществамодифицированное высвобождениесистемы направленной доставкифармакокинетикабиодоступностьexcipientsmodified releasedrug delivery systemspharmacokineticsbioavalabilityReferencesZhang M.-Q., Wilkinson B. Drug discovery beyond the „rule-of-five“. Curr. Opin. Biotechnol. 2007; 18: 6: 478-488.Zhang M.-Q., Wilkinson B. Drug discovery beyond the „rule-of-five“. Curr. Opin. Biotechnol. 2007; 18: 6: 478-488.Vistoli G., Pedretti A., Testa B. Assessing drug-likeness - what are we missing? Drug Discovery Today. 2008; 13: 7-8: 285-294.Vistoli G., Pedretti A., Testa B. Assessing drug-likeness - what are we missing? Drug Discovery Today. 2008; 13: 7-8: 285-294.Di L., Fish P. V., Mano T. Bridging solubility between drug discovery and development. Drug Discovery Today. 2012; 17: 9: 486-495.Di L., Fish P. V., Mano T. Bridging solubility between drug discovery and development. Drug Discovery Today. 2012; 17: 9: 486-495.Kang H.C., Huh K.M., Bae Y.H. Polymeric nucleic acid carriers: current issues and novel design approaches. J. Controlled Release. 2012; 164: 3: 256-264.Kang H.C., Huh K.M., Bae Y.H. Polymeric nucleic acid carriers: current issues and novel design approaches. J. Controlled Release. 2012; 164: 3: 256-264.Prakash S., Malhotra M., Shao W. et al. Polymeric nanohybrids and functionalized carbon nanotubes as drug delivery carriers for cancer therapy. Adv. Drug Deliver. Rev. 2011; 63: 14: 1340-1351.Prakash S., Malhotra M., Shao W. et al. Polymeric nanohybrids and functionalized carbon nanotubes as drug delivery carriers for cancer therapy. Adv. Drug Deliver. Rev. 2011; 63: 14: 1340-1351.Felber A.E., Bay?-Puxan N., Deleavey G.F. et. al. The interactions of amphiphilic antisense oligonucleotides with serum proteins and their effects on in vitro silencing activity. Biomaterials. 2012; 33: 25: 5955-5965.Felber A.E., Bay?-Puxan N., Deleavey G.F. et. al. The interactions of amphiphilic antisense oligonucleotides with serum proteins and their effects on in vitro silencing activity. Biomaterials. 2012; 33: 25: 5955-5965.Yamashita F., Hashida M. Pharmacokinetic considerations for targeted drug delivery. Adv. Drug Deliver. Rev. 2013; 65: 1: 139-147.Yamashita F., Hashida M. Pharmacokinetic considerations for targeted drug delivery. Adv. Drug Deliver. Rev. 2013; 65: 1: 139-147.Hunter A.C., Elsom J, Wibroe P.P., Moghimi S.M. Polymeric particulate technologies for oral drug delivery and targeting: a pathophysiological perspective. Nanomedicine: Nanotechnology, Biol. Med. 2012; 8: S5-S20.Hunter A.C., Elsom J, Wibroe P.P., Moghimi S.M. Polymeric particulate technologies for oral drug delivery and targeting: a pathophysiological perspective. Nanomedicine: Nanotechnology, Biol. Med. 2012; 8: S5-S20.Yousefi A., Storm G., Schiffelers R., Mastrobattista E. Trends in polymeric delivery of nucleic acids to tumors. J. Controlled Release. 2013; 170: 2: 209-218.Yousefi A., Storm G., Schiffelers R., Mastrobattista E. Trends in polymeric delivery of nucleic acids to tumors. J. Controlled Release. 2013; 170: 2: 209-218.Chen M.-C, Mi F.-L., Liao Z.-X. et. al. Recent advances in chitosan-based nanoparticles for oral delivery of macromolecules. Adv. Drug Delivery Rev. 2013; 65: 6: 865-879.Chen M.-C, Mi F.-L., Liao Z.-X. et. al. Recent advances in chitosan-based nanoparticles for oral delivery of macromolecules. Adv. Drug Delivery Rev. 2013; 65: 6: 865-879.Lalatsa A., Schätzlein A.G., Mazza M. et. al. Amphiphilic poly (l-amino acids) - new materials for drug delivery. J. Controlled Release. 2012; 161: 2: 523-536.Lalatsa A., Schätzlein A.G., Mazza M. et. al. Amphiphilic poly (l-amino acids) - new materials for drug delivery. J. Controlled Release. 2012; 161: 2: 523-536.Li J., Huo M., Wang J., Zhou J. et. al. Redox-sensitive micelles self-assembled from amphiphilic hyaluronic acid-deoxycholic acid conjugates for targeted intracellular delivery of paclitaxel. Biomater. 2012; 33: 7: 2310-2320.Li J., Huo M., Wang J., Zhou J. et. al. Redox-sensitive micelles self-assembled from amphiphilic hyaluronic acid-deoxycholic acid conjugates for targeted intracellular delivery of paclitaxel. Biomater. 2012; 33: 7: 2310-2320.Mishra D., Kang H.C., Bae Y.H. Reconstitutable charged polymeric (PLGA) 2-b-PEI micelles for gene therapeutics delivery. Biomater. 2011; 32: 15: 3845-3854.Mishra D., Kang H.C., Bae Y.H. Reconstitutable charged polymeric (PLGA) 2-b-PEI micelles for gene therapeutics delivery. Biomater. 2011; 32: 15: 3845-3854.Chen M-L. Lipid excipients and delivery systems for pharmaceutical development: a regulatory perspective. Adv. Drug Delivery Rev. 2008; 60: 6: 768-777.Chen M-L. Lipid excipients and delivery systems for pharmaceutical development: a regulatory perspective. Adv. Drug Delivery Rev. 2008; 60: 6: 768-777.Pilcer G., Amighi K. Formulation strategy and use of excipients in pulmonary drug delivery. Int. J. Pharm. 2010; 392: 1: 1-19.Pilcer G., Amighi K. Formulation strategy and use of excipients in pulmonary drug delivery. Int. J. Pharm. 2010; 392: 1: 1-19.Алексеев К.В., Тихонова Н.В., Блынская Е.В. и др. Технология повышения биологической и фармацевстической доступности лекарственных веществ. Вестник новых медицинских технологий. 2012; 9: 4: 43-47.Алексеев К.В., Тихонова Н.В., Блынская Е.В. и др. Технология повышения биологической и фармацевстической доступности лекарственных веществ. Вестник новых медицинских технологий. 2012; 9: 4: 43-47.Lee C.H., Kim J.-H., Lee H.J. et. al. The generation of iPS cells using non-viral magnetic nanoparticlebased transfection. Biomater. 2011; 32: 28: 6683-6691.Lee C.H., Kim J.-H., Lee H.J. et. al. The generation of iPS cells using non-viral magnetic nanoparticlebased transfection. Biomater. 2011; 32: 28: 6683-6691.Shirsand S.B., Ramani R.G., Swamy P.V Novel co-processed superdisintegrants in the design of fast dissolving tablets. Int. J. Pharma & Bio Sciences. 2010; 1: 1: 1-12.Shirsand S.B., Ramani R.G., Swamy P.V Novel co-processed superdisintegrants in the design of fast dissolving tablets. Int. J. Pharma & Bio Sciences. 2010; 1: 1: 1-12.Hamid K.A., Katsumi H., Sakane T., Yamamoto A. The effects of common solubilizing agents on the intestinal membrane barrier functions and membrane toxicity in rats. Int. J. Pharm. 2009; 379: 1: 100-108.Hamid K.A., Katsumi H., Sakane T., Yamamoto A. The effects of common solubilizing agents on the intestinal membrane barrier functions and membrane toxicity in rats. Int. J. Pharm. 2009; 379: 1: 100-108.Beig A., Miller J.M., Dahan A. Accounting for the solubility - permeability interplay in oral formulation development for poor water solubility drugs: the effect of PEG-400 on carbamazepine absorption. Eur. J. Pharm. Biopharm. 2012; 81: 2: 386-391.Beig A., Miller J.M., Dahan A. Accounting for the solubility - permeability interplay in oral formulation development for poor water solubility drugs: the effect of PEG-400 on carbamazepine absorption. Eur. J. Pharm. Biopharm. 2012; 81: 2: 386-391.Jannin V., Rodier J-D., Musakhanian J. Polyoxylglycerides and glycerides: Effects of manufacturing parameters on API stability, excipient functionality and processing. Int. J. Pharm. 2014; 466: 1: 109-121.Jannin V., Rodier J-D., Musakhanian J. Polyoxylglycerides and glycerides: Effects of manufacturing parameters on API stability, excipient functionality and processing. Int. J. Pharm. 2014; 466: 1: 109-121.Baki G., Bajdik J., Kelemen A., Pintye-H?di K. Formulation of a solid intravaginal matrix system to prolong the pH-decreasing effect of lactic acid. J. Drug Delivery Sci. Technol. 2009; 19: 2: 133-137.Baki G., Bajdik J., Kelemen A., Pintye-H?di K. Formulation of a solid intravaginal matrix system to prolong the pH-decreasing effect of lactic acid. J. Drug Delivery Sci. Technol. 2009; 19: 2: 133-137.Hu S.-G., Jou C-H., Yang M. Protein adsorption, fibroblast activity and antibacterial properties of poly (3-hydroxybutyric acid-co-3-hydroxy valeric acid) grafted with chitosan and chitooligosaccharide after immobilized with hyaluronic acid. Biomater. 2003; 24: 16: 2685-2693.Hu S.-G., Jou C-H., Yang M. Protein adsorption, fibroblast activity and antibacterial properties of poly (3-hydroxybutyric acid-co-3-hydroxy valeric acid) grafted with chitosan and chitooligosaccharide after immobilized with hyaluronic acid. Biomater. 2003; 24: 16: 2685-2693.Goole J., Lindley D.J., Roth W. et. al. The effects of excipients on transporter mediated absorption. Int. J. Pharm. 2010; 393: 1: 17-31.Goole J., Lindley D.J., Roth W. et. al. The effects of excipients on transporter mediated absorption. Int. J. Pharm. 2010; 393: 1: 17-31.Carrier R.L., Miller L.A., Ahmed I. The utility of cyclodextrins for enhancing oral bioavailability. J. Controlled Release. 2007; 123: 2: 78-99.Carrier R.L., Miller L.A., Ahmed I. The utility of cyclodextrins for enhancing oral bioavailability. J. Controlled Release. 2007; 123: 2: 78-99.Sarode A.L., Wang P., Obara S., Worthen D.R. Supersaturation, nucleation, and crystal growth during single-and biphasic dissolution of amorphous solid dispersions: Polymer effects and implications for oral bioavailability enhancement of poorly water soluble drugs. Eur. J. Pharm. Biopharm. 2014; 86: 3: 351-360.Sarode A.L., Wang P., Obara S., Worthen D.R. Supersaturation, nucleation, and crystal growth during single-and biphasic dissolution of amorphous solid dispersions: Polymer effects and implications for oral bioavailability enhancement of poorly water soluble drugs. Eur. J. Pharm. Biopharm. 2014; 86: 3: 351-360.Bhatt D., Maheria K., Parikh J. Mixed system of ionic liquid and non-ionic surfactants in aqueous media: Surface and thermodynamic properties. J. Chem. Thermodyn. 2014; 74: 184-192.Bhatt D., Maheria K., Parikh J. Mixed system of ionic liquid and non-ionic surfactants in aqueous media: Surface and thermodynamic properties. J. Chem. Thermodyn. 2014; 74: 184-192.Ouellet-Plamondon C.M., Stasiak J., Al-Tabbaa A. The effect of cationic, non-ionic and amphiphilic surfactants on the intercalation of bentonite. Colloids Surf., A: Physicochem. Eng. Aspects. 2014; 444: 330-337.Ouellet-Plamondon C.M., Stasiak J., Al-Tabbaa A. The effect of cationic, non-ionic and amphiphilic surfactants on the intercalation of bentonite. Colloids Surf., A: Physicochem. Eng. Aspects. 2014; 444: 330-337.Rege B.D., Yu L.X., Hussain A.S., Polli J.E. Effect of common excipients on Caco-2 transport of low-permeability drugs. J. Pharm. Sci. 2001; 90: 11: 1776-1786.Rege B.D., Yu L.X., Hussain A.S., Polli J.E. Effect of common excipients on Caco-2 transport of low-permeability drugs. J. Pharm. Sci. 2001; 90: 11: 1776-1786.Wagner D., Spahn-Langguth H., Hanafy A. et. al. Intestinal drug efflux: formulation and food effects. Adv. Drug Deliver. Rev. 2001; 50: S13-S31.Wagner D., Spahn-Langguth H., Hanafy A. et. al. Intestinal drug efflux: formulation and food effects. Adv. Drug Deliver. Rev. 2001; 50: S13-S31.Yamagata T., Kusuhara H., Morishita M. et. al. Improvement of the oral drug absorption of topotecan through the inhibition of intestinal xenobiotic efflux transporter, breast cancer resistance protein, by excipients. Drug Metab. Dispos. 2007; 35: 7: 1142-1148.Yamagata T., Kusuhara H., Morishita M. et. al. Improvement of the oral drug absorption of topotecan through the inhibition of intestinal xenobiotic efflux transporter, breast cancer resistance protein, by excipients. Drug Metab. Dispos. 2007; 35: 7: 1142-1148.Batrakova E.V., Li S., Li Y. et. al. Effect of pluronic P85 on ATPase activity of drug efflux transporters. Pharm. Res. 2004; 21: 12: 2226-2233.Batrakova E.V., Li S., Li Y. et. al. Effect of pluronic P85 on ATPase activity of drug efflux transporters. Pharm. Res. 2004; 21: 12: 2226-2233.Krylova O.O., Pohl P. Ionophoric activity of pluronic block copolymers. Biochem. 2004; 43: 12: 3696-3703.Krylova O.O., Pohl P. Ionophoric activity of pluronic block copolymers. Biochem. 2004; 43: 12: 3696-3703.Tayrouz Y. Pharmacokinetic and pharmaceutic interaction between digoxin and Cremophor RH40. Clin. Pharmacol. Ther. 2003; 73: 5: 397-405.Tayrouz Y. Pharmacokinetic and pharmaceutic interaction between digoxin and Cremophor RH40. Clin. Pharmacol. Ther. 2003; 73: 5: 397-405.Challa R., Ahuja A., Ali J., Khar R.K. Cyclodextrins in drug delivery: an updated review. Aaps Pharmscitech. 2005; 6: 2: E329-E357.Challa R., Ahuja A., Ali J., Khar R.K. Cyclodextrins in drug delivery: an updated review. Aaps Pharmscitech. 2005; 6: 2: E329-E357.Loftsson T., Brewster M.E. Pharmaceutical applications of cyclodextrins: basic science and product development. J. Pharm. Pharmacol. 2010; 62: 11: 1607-1621.Loftsson T., Brewster M.E. Pharmaceutical applications of cyclodextrins: basic science and product development. J. Pharm. Pharmacol. 2010; 62: 11: 1607-1621.Brewster M. E., Vandecruys R., Peeters J. et. al. Comparative interaction of 2-hydroxypropyl-ß-cyclodextrin and sulfobutylether-ß-cyclodextrin with itraconazole: phase-solubility behavior and stabilization of supersaturated drug solutions. Eur. J. Pharm. Sci. 2008; 34: 2: 94-103.Brewster M. E., Vandecruys R., Peeters J. et. al. Comparative interaction of 2-hydroxypropyl-ß-cyclodextrin and sulfobutylether-ß-cyclodextrin with itraconazole: phase-solubility behavior and stabilization of supersaturated drug solutions. Eur. J. Pharm. Sci. 2008; 34: 2: 94-103.Kurkov S. V., Madden D.E., Carr D., Loftsson T. The effect of parenterally administered cyclodextrins on the pharmacokinetics of coadministered drugs. J. Pharm. Sci. 2012; 101: 12: 4402-4408.Kurkov S. V., Madden D.E., Carr D., Loftsson T. The effect of parenterally administered cyclodextrins on the pharmacokinetics of coadministered drugs. J. Pharm. Sci. 2012; 101: 12: 4402-4408.Di Cagno M., Luppi B. Drug «supersaturation» states induced by polymeric micelles and liposomes: A mechanistic investigation into permeability enhancements. Eur. J. Pharm. Sci. 2013; 48: 4: 775-780.Di Cagno M., Luppi B. Drug «supersaturation» states induced by polymeric micelles and liposomes: A mechanistic investigation into permeability enhancements. Eur. J. Pharm. Sci. 2013; 48: 4: 775-780.Suzuki H., Onishi H., Hisamatsu S. et. al. Acetaminophen-containing chewable tablets with suppressed bitterness and improved oral feeling. Int. J. Pharm. 2004; 278: 1: 51 - 61.Suzuki H., Onishi H., Hisamatsu S. et. al. Acetaminophen-containing chewable tablets with suppressed bitterness and improved oral feeling. Int. J. Pharm. 2004; 278: 1: 51 - 61.Yu G., Yang B., Ren W. et. al. A comparative analysis of four kinds of polysaccharides purified from Furcellaria lumbricalis. J. Ocean Univ. China. 2007; 6: 1: 16-20.Yu G., Yang B., Ren W. et. al. A comparative analysis of four kinds of polysaccharides purified from Furcellaria lumbricalis. J. Ocean Univ. China. 2007; 6: 1: 16-20.Dai S., Ravi P., Tam K.C. pH-Responsive polymers: synthesis, properties and applications. Soft Matter. 2008; 4: 3: 435-449.Dai S., Ravi P., Tam K.C. pH-Responsive polymers: synthesis, properties and applications. Soft Matter. 2008; 4: 3: 435-449.Luo Y., Teng Z., Wang X., Wang Q. Development of carboxymethyl chitosan hydrogel beads in alcohol-aqueous binary solvent for nutrient delivery applications. Food Hydrocolloids. 2013; 31: 2: 332-339.Luo Y., Teng Z., Wang X., Wang Q. Development of carboxymethyl chitosan hydrogel beads in alcohol-aqueous binary solvent for nutrient delivery applications. Food Hydrocolloids. 2013; 31: 2: 332-339.Sonia T.A., Sharma C.P. An overview of natural polymers for oral insulin delivery. Drug Discovery Today. 2012; 17: 13: 784-792.Sonia T.A., Sharma C.P. An overview of natural polymers for oral insulin delivery. Drug Discovery Today. 2012; 17: 13: 784-792.Aryal M., Arvanitis C.D., Alexander P.M., McDannold N. Ultrasound-mediated blood-brain barrier disruption for targeted drug delivery in the central nervous system. Adv. Drug Deliver. Rev. 2014; 72: 94-109.Aryal M., Arvanitis C.D., Alexander P.M., McDannold N. Ultrasound-mediated blood-brain barrier disruption for targeted drug delivery in the central nervous system. Adv. Drug Deliver. Rev. 2014; 72: 94-109.Raveendran S., Yoshida Y., Maekawa T., Kumar D.S. Pharmaceutically versatile sulfated polysaccharide based bionano platforms. Nanomedicine: Nanotechnology, Biology and Medicine. 2013; 9: 5: 605-626.Raveendran S., Yoshida Y., Maekawa T., Kumar D.S. Pharmaceutically versatile sulfated polysaccharide based bionano platforms. Nanomedicine: Nanotechnology, Biology and Medicine. 2013; 9: 5: 605-626.Jayakumar R., Prabaharan M., Sudheesh Kumar P.T. et. al. Biomaterials based on chitin and chitosan in wound dressing applications. Biotechnol. Adv. 2011; 29: 3: 322-337.Jayakumar R., Prabaharan M., Sudheesh Kumar P.T. et. al. Biomaterials based on chitin and chitosan in wound dressing applications. Biotechnol. Adv. 2011; 29: 3: 322-337.Kean T., Thanou M. Biodegradation, biodistribution and toxicity of chitosan. Adv. Drug Deliver. Rev. 2010; 62: 1: 3-11.Kean T., Thanou M. Biodegradation, biodistribution and toxicity of chitosan. Adv. Drug Deliver. Rev. 2010; 62: 1: 3-11.Elzatahry A.A., Mohy Eldin M.S., Soliman E.A., Hassan E.A. Evaluation of alginate-chitosan bioadhesive beads as a drug delivery system for the controlled release of theophylline. J. Appl. Polym. Sci. 2009; 111: 5: 2452-2459.Elzatahry A.A., Mohy Eldin M.S., Soliman E.A., Hassan E.A. Evaluation of alginate-chitosan bioadhesive beads as a drug delivery system for the controlled release of theophylline. J. Appl. Polym. Sci. 2009; 111: 5: 2452-2459.Boddohi S., Moore N., Johnson P.A., Kipper M.J. Polysaccharide-based polyelectrolyte complex nanoparticles from chitosan, heparin, and hyaluronan. Biomacromolecules. 2009; 10: 6: 1402-1409.Boddohi S., Moore N., Johnson P.A., Kipper M.J. Polysaccharide-based polyelectrolyte complex nanoparticles from chitosan, heparin, and hyaluronan. Biomacromolecules. 2009; 10: 6: 1402-1409.Mi F.-L., Tan Y.-C., Liang H.-C. et. al. In vitro evaluation of a chitosan membrane cross-linked with genipin. J. Biomater. Sci., Polym. Ed. 2001; 12: 8: 835-850.Mi F.-L., Tan Y.-C., Liang H.-C. et. al. In vitro evaluation of a chitosan membrane cross-linked with genipin. J. Biomater. Sci., Polym. Ed. 2001; 12: 8: 835-850.Shi J., Liu X., Shang Y., Cao S. Biomineralized polysaccharide alginate membrane for multi-responsive controlled drug delivery. J. Membrane Sci. 2010; 352: 1: 262-270.Shi J., Liu X., Shang Y., Cao S. Biomineralized polysaccharide alginate membrane for multi-responsive controlled drug delivery. J. Membrane Sci. 2010; 352: 1: 262-270.Chen T.W., Chang S.J., Niu G.C.-C., Hsu Y.T., Kuo S.M. Alginate?coated chitosan membrane for guided tissue regeneration. J. Appl. Polym. Sci. 2006; 102: 5: 4528-4534.Chen T.W., Chang S.J., Niu G.C.-C., Hsu Y.T., Kuo S.M. Alginate?coated chitosan membrane for guided tissue regeneration. J. Appl. Polym. Sci. 2006; 102: 5: 4528-4534.George M., Abraham T.E. Polyionic hydrocolloids for the intestinal delivery of protein drugs: alginate and chitosan - a review. J. Controlled Release. 2006; 114: 1: 1-14.George M., Abraham T.E. Polyionic hydrocolloids for the intestinal delivery of protein drugs: alginate and chitosan - a review. J. Controlled Release. 2006; 114: 1: 1-14.Luo Y., Wang Q. Recent development of chitosan-based polyelectrolyte complexes with natural polysaccharides for drug delivery. Int. J. Biol. Macromol. 2014; 64: 353-367.Luo Y., Wang Q. Recent development of chitosan-based polyelectrolyte complexes with natural polysaccharides for drug delivery. Int. J. Biol. Macromol. 2014; 64: 353-367.Gong R., Li C., Zhu S. et. al. A novel pH-sensitive hydrogel based on dual crosslinked alginate/N-a-glutaric acid chitosan for oral delivery of protein. Carbohydr. Polym. 2011; 85: 4: 869-874.Gong R., Li C., Zhu S. et. al. A novel pH-sensitive hydrogel based on dual crosslinked alginate/N-a-glutaric acid chitosan for oral delivery of protein. Carbohydr. Polym. 2011; 85: 4: 869-874.Joshi A., Solanki S., Chaudhari R. et. al. Multifunctional alginate microspheres for biosensing, drug delivery and magnetic resonance imaging. Acta Biomaterialia. 2011; 7: 11: 3955-3963.Joshi A., Solanki S., Chaudhari R. et. al. Multifunctional alginate microspheres for biosensing, drug delivery and magnetic resonance imaging. Acta Biomaterialia. 2011; 7: 11: 3955-3963.Ribeiro A. J., Silva C., Ferreira D., Veiga F. Chitosan-reinforced alginate microspheres obtained through the emulsification/internal gelation technique. Eur. J. Pharm. Sci. 2005; 25: 1: 31-40.Ribeiro A. J., Silva C., Ferreira D., Veiga F. Chitosan-reinforced alginate microspheres obtained through the emulsification/internal gelation technique. Eur. J. Pharm. Sci. 2005; 25: 1: 31-40.Vandenberg G. W., Drolet C., Scott S.L., de la No?e J. Factors affecting protein release from alginate-chitosan coacervate microcapsules during production and gastric/intestinal simulation. J. Controlled Release. 2001; 77: 3: 297-307.Vandenberg G. W., Drolet C., Scott S.L., de la No?e J. Factors affecting protein release from alginate-chitosan coacervate microcapsules during production and gastric/intestinal simulation. J. Controlled Release. 2001; 77: 3: 297-307.Yang L., Liu H. Stimuli-responsive magnetic particles and their applications in biomedical field. Powder Technol. 2013; 240: 54-65.Yang L., Liu H. Stimuli-responsive magnetic particles and their applications in biomedical field. Powder Technol. 2013; 240: 54-65.Sæther H.V., Holme H.K., Maurstad G. et. al. Polyelectrolyte complex formation using alginate and chitosan. Carbohydr. Polym. 2008; 74: 4: 813-821.Sæther H.V., Holme H.K., Maurstad G. et. al. Polyelectrolyte complex formation using alginate and chitosan. Carbohydr. Polym. 2008; 74: 4: 813-821.Liu H.-J., Li P., Wei Q. Magnetic N-succinyl chitosan/alginate beads for carbamazepine delivery. Drug Dev. Ind. Pharm. 2010; 36: 11: 1286-1294.Liu H.-J., Li P., Wei Q. Magnetic N-succinyl chitosan/alginate beads for carbamazepine delivery. Drug Dev. Ind. Pharm. 2010; 36: 11: 1286-1294.Zhang Y., Wei W., Lv P. et. al. Preparation and evaluation of alginate-chitosan microspheres for oral delivery of insulin. Eur. J. Pharm. Biopharm. 2011; 77: 1: 11-19.Zhang Y., Wei W., Lv P. et. al. Preparation and evaluation of alginate-chitosan microspheres for oral delivery of insulin. Eur. J. Pharm. Biopharm. 2011; 77: 1: 11-19.Tavakol M., Vasheghani-Farahani E., Dolatabadi-Farahani T., Hashemi-Najafabadi S. Sulfasalazine release from alginate-N, O-carboxymethyl chitosan gel beads coated by chitosan. Carbohydr. Polym. 2009; 77: 2: 326-330.Tavakol M., Vasheghani-Farahani E., Dolatabadi-Farahani T., Hashemi-Najafabadi S. Sulfasalazine release from alginate-N, O-carboxymethyl chitosan gel beads coated by chitosan. Carbohydr. Polym. 2009; 77: 2: 326-330.Motwani S.K., Chopra S., Talegaonkar S. et. al. Chitosan-sodium alginate nanoparticles as submicroscopic reservoirs for ocular delivery: Formulation, optimisation and in vitro characterization. Eur. J. Pharm. Biopharm. 2008; 68: 3: 513-525.Motwani S.K., Chopra S., Talegaonkar S. et. al. Chitosan-sodium alginate nanoparticles as submicroscopic reservoirs for ocular delivery: Formulation, optimisation and in vitro characterization. Eur. J. Pharm. Biopharm. 2008; 68: 3: 513-525.Wong T.W., Chan L.W., Kho S.B., Sia Heng P.W. Design of controlled-release solid dosage forms of alginate and chitosan using microwave. J. Controlled Release. 2002; 84: 3: 99-114.Wong T.W., Chan L.W., Kho S.B., Sia Heng P.W. Design of controlled-release solid dosage forms of alginate and chitosan using microwave. J. Controlled Release. 2002; 84: 3: 99-114.Zhao Q. S., Ji Q. X., ChengX. J. et. al. Preparation of alginate coated chitosan hydrogel beads by thermosensitive internal gelation technique. J. Sol-Gel Sci. Technol. 2010; 54: 2: 232-237.Zhao Q. S., Ji Q. X., ChengX. J. et. al. Preparation of alginate coated chitosan hydrogel beads by thermosensitive internal gelation technique. J. Sol-Gel Sci. Technol. 2010; 54: 2: 232-237.Das R.K., Kasoju N., Bora U. Encapsulation of curcumin in alginate-chitosan-pluronic composite nanoparticles for delivery to cancer cells. Nanomedicine: Nanotechnology, Biology and Medicine. 2010; 6: 1: 153-160.Das R.K., Kasoju N., Bora U. Encapsulation of curcumin in alginate-chitosan-pluronic composite nanoparticles for delivery to cancer cells. Nanomedicine: Nanotechnology, Biology and Medicine. 2010; 6: 1: 153-160.El-Sherbiny I.M. Enhanced pH-responsive carrier system based on alginate and chemically modified carboxymethyl chitosan for oral delivery of protein drugs: preparation and in-vitro assessment. Carbohydr. Polym. 2010; 80: 4: 1125-1136.El-Sherbiny I.M. Enhanced pH-responsive carrier system based on alginate and chemically modified carboxymethyl chitosan for oral delivery of protein drugs: preparation and in-vitro assessment. Carbohydr. Polym. 2010; 80: 4: 1125-1136.Ridley B.L., O’Neill M.A., Mohnen D. Pectins: structure, biosynthesis, and oligogalacturonide-related signaling. Phytochem. 2001; 57: 6: 929-967.Ridley B.L., O’Neill M.A., Mohnen D. Pectins: structure, biosynthesis, and oligogalacturonide-related signaling. Phytochem. 2001; 57: 6: 929-967.Sinha R., Kumria R. Polysaccharides in colon-specific drug delivery. Int. J. Pharm. 2001; 224: 1: 19-38.Sinha R., Kumria R. Polysaccharides in colon-specific drug delivery. Int. J. Pharm. 2001; 224: 1: 19-38.Sriamornsak P. Application of pectin in oral drug delivery. Expert Opin. Drug Deliver. 2011; 8: 8: 1009-1023.Sriamornsak P. Application of pectin in oral drug delivery. Expert Opin. Drug Deliver. 2011; 8: 8: 1009-1023.Wittaya-areekul S., Kruenate J., Prahsarn C. Preparation and in vitro evaluation of mucoadhesive properties of alginate/chitosan microparticles containing prednisolone. Int. J. Pharm. 2006; 312: 1: 113-118.Wittaya-areekul S., Kruenate J., Prahsarn C. Preparation and in vitro evaluation of mucoadhesive properties of alginate/chitosan microparticles containing prednisolone. Int. J. Pharm. 2006; 312: 1: 113-118.Prajapati V.D., Maheriya P.M., Jani G.K., Solanki H.K. Carrageenan: a natural seaweed polysaccharide and its applications. Carbohydr. Polym. 2014; 105: 97-112.Prajapati V.D., Maheriya P.M., Jani G.K., Solanki H.K. Carrageenan: a natural seaweed polysaccharide and its applications. Carbohydr. Polym. 2014; 105: 97-112.Piyakulawat P., Praphairaksit N., Chantarasiri N., Muangsin N. Preparation and evaluation of chitosan/carrageenan beads for controlled release of sodium diclofenac. Aaps PharmSciTech. 2007; 8: 4: 120-130.Piyakulawat P., Praphairaksit N., Chantarasiri N., Muangsin N. Preparation and evaluation of chitosan/carrageenan beads for controlled release of sodium diclofenac. Aaps PharmSciTech. 2007; 8: 4: 120-130.Amiji M.M. Synthesis of anionic poly (ethylene glycol) derivative for chitosan surface modification in blood-contacting applications. Carbohydr. Polym. 1997; 32: 3: 193-199.Amiji M.M. Synthesis of anionic poly (ethylene glycol) derivative for chitosan surface modification in blood-contacting applications. Carbohydr. Polym. 1997; 32: 3: 193-199.Ekici S., Ilgin P., Butun S., Sahiner N. Hyaluronic acid hydrogel particles with tunable charges as potential drug delivery devices. Carbohydr. Polym. 2011; 84: 4: 1306-1313.Ekici S., Ilgin P., Butun S., Sahiner N. Hyaluronic acid hydrogel particles with tunable charges as potential drug delivery devices. Carbohydr. Polym. 2011; 84: 4: 1306-1313.Xu X., Jha A.K., Harrington D.A. et. al. Hyaluronic acid-based hydrogels: from a natural polysaccharide to complex networks. Soft Matter. 2012; 8: 12: 3280-3294.Xu X., Jha A.K., Harrington D.A. et. al. Hyaluronic acid-based hydrogels: from a natural polysaccharide to complex networks. Soft Matter. 2012; 8: 12: 3280-3294.Pérez R.A., Won J.-E., Knowles J.C., Kim H.-W. Naturally and synthetic smart composite biomaterials for tissue regeneration. Adv. Drug Deliver. Rev. 2013; 65: 4: 471-496.Pérez R.A., Won J.-E., Knowles J.C., Kim H.-W. Naturally and synthetic smart composite biomaterials for tissue regeneration. Adv. Drug Deliver. Rev. 2013; 65: 4: 471-496.Contreras-Ruiz L., de la Fuente M., García- Vázquez C. et. al. Ocular tolerance to a topical formulation of hyaluronic acid and chitosan-based nanoparticles. Cornea. 2010; 29: 5: 550-558.Contreras-Ruiz L., de la Fuente M., García- Vázquez C. et. al. Ocular tolerance to a topical formulation of hyaluronic acid and chitosan-based nanoparticles. Cornea. 2010; 29: 5: 550-558.Manna U., Bharani S., Patil S. Layer-by-layer self-assembly of modified hyaluronic acid/chitosan based on hydrogen bonding. Biomacromol. 2009; 10: 9: 2632-2639.Manna U., Bharani S., Patil S. Layer-by-layer self-assembly of modified hyaluronic acid/chitosan based on hydrogen bonding. Biomacromol. 2009; 10: 9: 2632-2639.Tan R., She Z., Wang M. et. al. Thermo-sensitive alginate-based injectable hydrogel for tissue engineering. Carbohydr. Polym. 2012; 87: 2: 1515-1521.Tan R., She Z., Wang M. et. al. Thermo-sensitive alginate-based injectable hydrogel for tissue engineering. Carbohydr. Polym. 2012; 87: 2: 1515-1521.Ji C., Khademhosseini A., Dehghani F. Enhancing cell penetration and proliferation in chitosan hydrogels for tissue engineering applications. Biomater. 2011; 32: 36: 9719-9729.Ji C., Khademhosseini A., Dehghani F. Enhancing cell penetration and proliferation in chitosan hydrogels for tissue engineering applications. Biomater. 2011; 32: 36: 9719-9729.García-Ochoa F., Santos V.E., Casas J.A., Gómez E. Xanthan gum: production, recovery, and properties. Biotechnol. Adv. 2000; 18: 7: 549-579.García-Ochoa F., Santos V.E., Casas J.A., Gómez E. Xanthan gum: production, recovery, and properties. Biotechnol. Adv. 2000; 18: 7: 549-579.Phaechamud T., Ritthidej G.C. Sustained-release from layered matrix system comprising chitosan and xanthan gum. Drug Dev. Ind. Pharm. 2007; 33: 6: 595-605.Phaechamud T., Ritthidej G.C. Sustained-release from layered matrix system comprising chitosan and xanthan gum. Drug Dev. Ind. Pharm. 2007; 33: 6: 595-605.Liu H., Nakagawa K., Kato D. et. al. Enzyme encapsulation in freeze-dried bionanocomposites prepared from chitosan and xanthan gum blend. Mater. Chem. Phys. 2011; 129: 1: 488-494.Liu H., Nakagawa K., Kato D. et. al. Enzyme encapsulation in freeze-dried bionanocomposites prepared from chitosan and xanthan gum blend. Mater. Chem. Phys. 2011; 129: 1: 488-494.Giavasis I., Harvey L.M., McNeil B. Gellan gum. Crit. Rev. Biotechnol. 2000; 20: 3: 177-211.Giavasis I., Harvey L.M., McNeil B. Gellan gum. Crit. Rev. Biotechnol. 2000; 20: 3: 177-211.Silva-Correia J., Oliveira J.M., Caridade S.G. et. al. Gellan gum-based hydrogels for intervertebral disc tissue?engineering applications. J. Tissue Eng. Regenerative Med. 2011; 5: 6: e97-e107.Silva-Correia J., Oliveira J.M., Caridade S.G. et. al. Gellan gum-based hydrogels for intervertebral disc tissue?engineering applications. J. Tissue Eng. Regenerative Med. 2011; 5: 6: e97-e107.Prajapati V D., Jani G.K., Zala B.S., Khutliwala T.A. An insight into the emerging exopolysaccharide gellan gum as a novel polymer. Carbohydr. Polym. 2013; 93: 2: 670-678.Prajapati V D., Jani G.K., Zala B.S., Khutliwala T.A. An insight into the emerging exopolysaccharide gellan gum as a novel polymer. Carbohydr. Polym. 2013; 93: 2: 670-678.Ali B.H., Ziada A., Blunden G. Biological effects of gum arabic: a review of some recent research. Food Chem. Toxicol. 2009; 47: 1: 1-8.Ali B.H., Ziada A., Blunden G. Biological effects of gum arabic: a review of some recent research. Food Chem. Toxicol. 2009; 47: 1: 1-8.Parenteau-Bareil R., Gauvin R., Berthod F. Collagen-based biomaterials for tissue engineering applications. Mater. 2010; 3: 3: 1863-1887.Parenteau-Bareil R., Gauvin R., Berthod F. Collagen-based biomaterials for tissue engineering applications. Mater. 2010; 3: 3: 1863-1887.Assaad E., Mateescu M.A. The influence of protonation ratio on properties of carboxymethyl starch excipient at various substitution degrees: Structural insights and drug release kinetics. Int. J. Pharm. 2010; 394: 1: 75-84.Assaad E., Mateescu M.A. The influence of protonation ratio on properties of carboxymethyl starch excipient at various substitution degrees: Structural insights and drug release kinetics. Int. J. Pharm. 2010; 394: 1: 75-84.Friciu M.M., Canh Le T., Ispas-Szabo P., Mateescu M.A. Carboxymethyl starch and lecithin complex as matrix for targeted drug delivery: I. Monolithic Mesalamine forms for colon delivery. Eur. J. Pharm. Biopharm. 2013; 85: 3: 521-530.Friciu M.M., Canh Le T., Ispas-Szabo P., Mateescu M.A. Carboxymethyl starch and lecithin complex as matrix for targeted drug delivery: I. Monolithic Mesalamine forms for colon delivery. Eur. J. Pharm. Biopharm. 2013; 85: 3: 521-530.Calinescu C., Nadeau É., Mulhbacher J., Fairbrother J.M., Mateescu M.-A. Carboxymethyl high amylose starch for F4 fimbriae gastro-resistant oral formulation. Int. J. Pharm. 2007; 343: 1: 18-25.Calinescu C., Nadeau É., Mulhbacher J., Fairbrother J.M., Mateescu M.-A. Carboxymethyl high amylose starch for F4 fimbriae gastro-resistant oral formulation. Int. J. Pharm. 2007; 343: 1: 18-25.Qureshi A.I., Cohen R.D. Mesalamine delivery systems: do they really make much difference? Adv. Drug Deliver. Rev. 2005; 57: 2: 281-302.Qureshi A.I., Cohen R.D. Mesalamine delivery systems: do they really make much difference? Adv. Drug Deliver. Rev. 2005; 57: 2: 281-302.Siepmann J., Peppas N.A. Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Adv. Drug Deliver. Rev. 2012; 64: 163-174.Siepmann J., Peppas N.A. Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Adv. Drug Deliver. Rev. 2012; 64: 163-174.Oishi M., Hayashi H., Iijima M., Nagasaki Y. Endosomal release and intracellular delivery of anticancer drugs using pH-sensitive PEGylated nanogels. J. Mater. Chem. 2007; 17: 35: 3720-3725.Oishi M., Hayashi H., Iijima M., Nagasaki Y. Endosomal release and intracellular delivery of anticancer drugs using pH-sensitive PEGylated nanogels. J. Mater. Chem. 2007; 17: 35: 3720-3725.Shim W.S., Kim J.-H., Park H. et. al. Biodegradability and biocompatibility of a pH-and thermo-sensitive hydrogel formed from a sulfonamide-modified poly (e-caprolactone-co-lactide)-poly (ethylene glycol)-poly (?-caprolactone-co-lactide) block copolymer. Biomater. 2006; 27: 30: 5178-5185.Shim W.S., Kim J.-H., Park H. et. al. Biodegradability and biocompatibility of a pH-and thermo-sensitive hydrogel formed from a sulfonamide-modified poly (e-caprolactone-co-lactide)-poly (ethylene glycol)-poly (?-caprolactone-co-lactide) block copolymer. Biomater. 2006; 27: 30: 5178-5185.Du J., Tang Y., Lewis A.L., Armes S.P. pH-sensitive biocompatible block copolymer vesicles for drug delivery. J. Controlled Release. 2011; 152: e16-e17.Du J., Tang Y., Lewis A.L., Armes S.P. pH-sensitive biocompatible block copolymer vesicles for drug delivery. J. Controlled Release. 2011; 152: e16-e17.Ho V.H.B., Slater N.K.H., Chen R. pH-responsive endosomolytic pseudo-peptides for drug delivery to multicellular spheroids tumour models. Biomater. 2011; 32: 11: 2953-2958.Ho V.H.B., Slater N.K.H., Chen R. pH-responsive endosomolytic pseudo-peptides for drug delivery to multicellular spheroids tumour models. Biomater. 2011; 32: 11: 2953-2958.Yuan C.-H., Lin S.-B., Liu B. et. al. Synthesis and characterization of poly (4-acetyl acryloyl ethyl acetate-co-acrylic acid) novel temperature/ pH-sensitive hydrogels. Sens. Actuators, B: Chem. 2009; 140: 1: 155-161.Yuan C.-H., Lin S.-B., Liu B. et. al. Synthesis and characterization of poly (4-acetyl acryloyl ethyl acetate-co-acrylic acid) novel temperature/ pH-sensitive hydrogels. Sens. Actuators, B: Chem. 2009; 140: 1: 155-161.Mu B., Liu P. Temperature and pH dual responsive crosslinked polymeric nanocapsules via surface-initiated atom transfer radical polymerization. React. Funct. Polym. 2012; 72: 12: 983-989.Mu B., Liu P. Temperature and pH dual responsive crosslinked polymeric nanocapsules via surface-initiated atom transfer radical polymerization. React. Funct. Polym. 2012; 72: 12: 983-989.Garbern J.C., Minami E., Stayton P.S., Murry C.E. Delivery of basic fibroblast growth factor with a pH-responsive, injectable hydrogel to improve angiogenesis in infarcted myocardium. Biomater. 2011; 32: 9: 2407-2416.Garbern J.C., Minami E., Stayton P.S., Murry C.E. Delivery of basic fibroblast growth factor with a pH-responsive, injectable hydrogel to improve angiogenesis in infarcted myocardium. Biomater. 2011; 32: 9: 2407-2416.

The authors declare that there are no conflicts of interest present.