Hierarchical porous bio polyurethane film as an implantable delivery system for sustained release of insulin: Synthesis, characterization, and in-vitro evaluation

Abstract

In this study, a novel star-hyperbranched polyurethane (SR-HPU) with a star-shaped glucose-based PHBV (GS-PHBV) core was synthesized for sustained-release of insulin. The successful synthesis of GS-PHBV, SR-HPU, and preparation of INS-PUF were confirmed by 1HNMR and ATR-IR analysis. Thermogravimetric analysis (TGA), X-Ray diffraction analysis (XRD), and water contact angle (WCA) analysis demonstrated that due to the block copolymerization of GS-PHBV with HDI and PEG, the crystalline patterns of the final films were disrupted, which led to an increase in their hydrophilicity. These results aligned with other findings from in vitro biodegradability and cytocompatibility studies of films as well. As a result, gravimetric measurements of the films in phosphate buffer solution (PBS) (pH 7.4 at 37°) revealed that SR-HPU lost more weight (∼28%) than GS-PHBV (∼4%) after 35 days of degradation, which was also in good agreement with the water contact angles of them (82.9° vs 58.4°). Also, the surface topographical changes of the porous structure before and after degradation were compared by field emission scanning electron microscopy (FESEM)micrographs. XRD and Energy dispersive X-ray (EDX) mapping results revealed that insulin is uniformly present within the highly porous SR-HPU matrix. In vitro cytotoxicity studies of films on (L929) indicated excellent biocompatibility with high cell viability and rapid cell proliferation. Moreover, the findings from the in vitro release studies of INS-PUF showed that a prolonged insulin release pattern had been achieved for 8 weeks and followed the Higuchi model.