A Novel Controlled Release Implant of Insulin Based on Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Polymer Prepared by Extrusion.

Objectives: The aim of this study was to develop a biodegradable implant with a slow release of insulin to minimize the amount of repeated drug injections in patients.Developing and designing implants with controlled release of active protein has always been a challenge. To optimize and control the release of insulin in this project, the drug complexing mechanism was used by dextran sulfate sodium (DS) and Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) polymer. Materials and Methods: The efficacy of drug binding was evaluated under different molecular ratios of DS, and then a thermogravimetric analysis test was done to check the stability of the drug complex in extrusion. In the final stage, rod-shaped implants of complexed insulin were prepared by an extrusion process, and the drug release was evaluated within 32 days. The drug release kinetics were evaluated using mathematical models. Results: The results showed an increase in insulin binding efficiency percent, up to a ratio of 2.6. The drug release from the implant containing complex insulin was completely controlled. The drug release followed a zero-order release model. Interestingly, the complex form of the drug showed a temperature resistance of 160 °C for ten minutes. Conclusion: In this study, for the first time, a controlled release implant of insulin has been developed based on a PHBV polymer. In this method, the extrusion process has been used, which provides the possibility of preparing implants on an industrial scale in the future. Also, their development appears to be a promising treatment for diabetic patients and leads to the elimination of frequent drug injections and then more adherence of the patients to the continuation of the treatment process.