Preparation of glucose responsive polyelectrolyte capsules with shell crosslinking via the layer-by-layer technique and sustained release of insulin

Abstract

Phenylboronic acid based polymer capsules were confirmed to have glucose sensitivity. In order to investigate the effect of the capsule structural stability on the glucose sensitivity and sustained release of insulin, bio-based capsules with a glucose-responsive property were fabricated based on alginate (Alg) and chitosan oligosaccharide (CS) polyelectrolytes. Chitosan oligosaccharide-g-3-carboxyphenylboronic acid (CS-g-CPBA) that has glucose-responsive properties was firstly synthesized by grafting CPBA to CS. (Alg/CS-g-CPBA_m)_n capsules were then prepared by layer-by-layer (LBL) processes of Alg and CS-g-CPBA_mvia electrostatic interaction on silica nanoparticles (SiO₂) and subsequently removing the SiO₂ templates. Capsules could be further crosslinked and kept more stable by chelating calcium ions (Ca²⁺). The sizes and morphologies of bio-polymer capsules were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The results showed that the (Alg/CS-g-CPBA_m)_n capsules had a good stability by increasing the multilayers and cross-linking with Ca²⁺. The size of the capsules increased rapidly with increasing the glucose concentration, due to the formation of a hydrophilic phenylboronic acid-glucose complex and swelling of the capsules. Insulin was encapsulated in the capsules, and the encapsulation efficiency was more than 65%. A cumulative release of insulin was observed from the capsules after being exposed in glucose solutions with various levels. The release speed of insulin reduced after it was cross-linked with Ca²⁺, which was induced by increasing the tightness of the inner layer. The (Alg/CS-g-CPBA_m)_n capsules have biocompatibility which was confirmed by cell viability on treatment with mouse embryonic fibroblast through the method of MTT.