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.