title: The Influence of Chitosan Cross-linking on the Properties of Alginate Microparticles with Metformin Hydrochloride-In Vitro and In Vivo Evaluation.
abstract: Sodium alginate is a polymer with unique ability to gel with different cross-linking agents in result of ionic and electrostatic interactions. Chitosan cross-linked alginate provides improvement of swelling and mucoadhesive properties and might be used to design sustained release dosage forms. Therefore, the aim of this research was to develop and evaluate possibility of preparing chitosan cross-linked alginate microparticles containing metformin hydrochloride by the spray-drying method. In addition, influence of cross-linking agent on the properties of microparticles was evaluated. Formulation of microparticles prepared by the spray drying of 2% alginate solution cross-linked by 0.1% chitosan was characterized by good mucoadhesive properties, high drug loading and prolonged metformin hydrochloride release. It was shown that designed microparticles reduced rat glucose blood level, delayed absorption of metformin hydrochloride and provided stable plasma drug concentration. Additionally, histopathological studies of pancreas, liver and kidneys indicated that all prepared microparticles improved degenerative changes in organs of diabetic rats. Moreover, no toxicity effect and no changes in rats behavior after oral administration of chitosan cross-linked alginate microparticles were noted.
authors.affiliation: Department of Pharmaceutical Technology, Medical University of Białystok, Mickiewicza 2c, Białystok 15-222, Poland. marta.szekalska@umb.edu.pl.
authors.forename: Marta
authors.initials: M
authors.lastname: Szekalska
authors.affiliation: Department of Pharmaceutical Technology, Medical University of Białystok, Mickiewicza 2c, Białystok 15-222, Poland. katarzyna.sosnowska@umb.edu.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Sosnowska
authors.affiliation: Department of Biopharmacy, Medical University of Białystok, Mickiewicza 2c, Białystok 15-222, Poland. azakrze@umb.edu.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Zakrzeska
authors.affiliation: Department of Histology and Cytophysiology, Medical University of Białystok, Mickiewicza 2c, Białystok 15-222, Poland. kasacka@umb.edu.pl.
authors.forename: Irena
authors.initials: I
authors.lastname: Kasacka
authors.affiliation: Department of Histology and Cytophysiology, Medical University of Białystok, Mickiewicza 2c, Białystok 15-222, Poland. alicja.lewandowska@umb.edu.pl.
authors.forename: Alicja
authors.initials: A
authors.lastname: Lewandowska
authors.affiliation: Department of Pharmaceutical Technology, Medical University of Białystok, Mickiewicza 2c, Białystok 15-222, Poland. kwin@umb.edu.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Winnicka
mesh_terms: D000464:Alginates / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry* / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000138:chemical synthesis* / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000188:drug therapy*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000494:pharmacology; D004339:Drug Compounding / Q000379:methods; D020723:Glucuronic Acid / Q000737:chemistry / Q000494:pharmacology; D006603:Hexuronic Acids / Q000737:chemistry / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D008687:Metformin / Q000737:chemistry* / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
chemical_list: D000464:Alginates; D001786:Blood Glucose; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006603:Hexuronic Acids; D013311:Streptozocin; D020723:Glucuronic Acid; D048271:Chitosan; D008687:Metformin
keywords: alginate; chitosan; cross-linking; hypoglycemic activity; metformin hydrochloride; microparticles; spray drying; toxicity