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.

Alginate Oligosaccharides Affect Mechanical Properties and Antifungal Activity of Alginate Buccal Films with Posaconazole

“…POS-release test was performed in SSS as a dissolution medium (pH 6.8) with physiological pH. At pH close to 7, the carboxylic groups of alginate ionize and become -COO-in form, which results in weakening the hydrogen bonding in the polymer chain and electrostatic repulsion from -COO− and higher swelling capacity [32,33]. Formulation F4, composed of only OLG, exhibited definitely higher POS-release, which was related to its swelling properties as they determined the solvent penetration into the matrix.…”

“…POS-release kinetic was evaluated based on five mathematical models: zero-order, first-order, Higuchi, Korsmeyer-Peppas, and Hixson-Crowell [17,33].…”

Advanced hydrogels for treatment of diabetes

“…Within the most popular class of biomaterials to address the limitations of diabetes therapy are glucose‐responsive hydrogels (Espona‐Noguera et al, ), sheets (Shimizu et al, ), nanoparticles (NPs; Gu et al, ; Szekalska et al, ), and glucose‐responsive microneedle patches (Seong et al, ; J. Yu et al, ). Overall, these materials have been developed to sense glucose (Shao et al, ), deliver insulin, and restore euglycemia (Gu et al, ; Seong et al, ; J. Yu et al, ).…”

“…Within the most popular class of biomaterials to address the limitations of diabetes therapy are glucose-responsive hydrogels (Espona-Noguera et al, 2017), sheets (Shimizu et al, 2009), nanoparticles (NPs; Gu et al, 2013;Szekalska et al, 2017), and glucose-responsive microneedle patches (Seong et al, 2017;J. Yu et al, 2015).…”

Microparticles Formulation as a Targeting Drug Delivery System

“…Two general principles are involved in retarding drug release from most practically prolonged action formulations involving dosage form modification. These are the barrier and the embedded matrix principle [19][20][21][22].…”