Sustained drug delivery system for insulin using supramolecular hydrogels composed of tri-block copolymers

Abstract

Formulating a polypeptide gastrointestinal drug delivery system have been persistent challenges. To overcome these challenges, in situ-forming gels are more attractive because of their biodegradability and easy preparation and administration. In this study, biodegradable triblock copolymer polycaprolactone–polyethylene glycol–polycaprolactone [PCL–PEG–PCL (PCEC)] was synthesized under microwave irradiation and their gelation with different concentrations of α-cyclodextrin (CD) was investigated. PCEC was characterized by 1HNMR and gel permeation chromatography. The hydrogel and copolymer were also evaluated using differential scanning colorimetery, X-ray diffraction study and scanning electron microscopy. Also rheological properties were investigated. Four different concentrations of hydrogels consisting of the copolymer [5 and 7.5% (w/w)] and α-CD [10 and 14% (w/w)] were studied to evaluate insulin cumulative release profiles during 37 days. Finally, CD spectrum and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) tests were performed to approve the stability of released insulin. It was demonstrated that the synthesis of PCEC via microwave irradiation was fast and efficient. Copolymer and α-CD concentrations are important in forming supramolecular hydrogels. Rheographs indicated the injectability and thixotropic behavior. In vitro release studies affirmed the sustained release profile of insulin. Both polymer degradation and drug diffusion are involved in it. Results of stability tests confirmed the stability of insulin following release.