The Influence of Chitosan Cross-linking on the Properties of Alginate Microparticles with Metformin Hydrochloride-In Vitro and In Vivo Evaluation.

Marta Szekalska,Alicja Lewandowska,Katarzyna Sosnowska,Agnieszka Zakrzeska,Katarzyna Winnicka,Irena Kasacka

doi:10.3390/molecules22010182

Marta Szekalska, Alicja Lewandowska + Show 4 more

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https://doi.org/10.3390/molecules22010182

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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.

Highlights

Sodium alginate (ALG) belongs to the group of polysaccharides naturally produced by seaweeds and bacteria [1,2]
The obtained results have shown that one-step spray-drying process might be successfully used to prepare microparticles using
The obtained data suggest that the spray-drying technique might be used to prepare chitosan cross-linked ALG microparticles with Metformin hydrochloride (MF) using 2% ALG solution and 0.1% or 0.05% chitosan as cross-linking agent

Summary

Introduction

Sodium alginate (ALG) belongs to the group of polysaccharides naturally produced by seaweeds and bacteria [1,2]. It is nontoxic, biocompatible and biodegradable polymer, which is composed of β-D-mannuronic acid and α-L-guluronic acid residues joined by (1–4) glycosidic linkages. ALG is characterized by swelling and mucoadhesive properties and possesses unique ability to gel [3]. Common used gelling method is ionic cross-linking process, which is known as “egg-box” model. Mechanism of this process includes binding of divalent or trivalent cations by the guluronate blocks of the polymer chain which provides gel forming. Calcium chloride (CaCl2 ) is one of the most frequently used ALG ionically cross-linking agents [3,4]

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