Injectable and biodegradable phospholipid-based phase separation gel for sustained delivery of insulin

Long-term and daily injection of insulin for the treatment of diabetes mellitus often bring great suffering to patients. In order to reduce injection frequency and improve patient compliance, an injectable in-situ forming phospholipid-based phase separation gel (PPSG) was formulated in the present study. Insulin was loaded into PPSG for sustained and controlled delivery, which could maintain the bioactivity of insulin during its release process. The in-situ formation and degradation behavior of PPSG in vivo indicated that solvent exchange could be the driving force for phase transition and that phospholipid vesicle formation and burst could be the mechanism of drug release and gel degradation. In the foreign body response study, PPSG implants were demonstrated to be biodegradable, and the degree of inflammation and fibrotic responses could be decreased by increasing the phospholipid content. The applicability of insulin on PPSG was justified by studying the drug release property and the bioactivity of insulin in PPSG. As a result, the insulin-loaded PPSG showed a sustained drug release behavior and a long-lasting hypoglycemic effect in diabetic rats. In conclusion, PPSG is of good biocompatibility and biodegradability, which is promising to serve as a sustained insulin delivery system and improve patient compliance effectively.