Synthesis of and Insulin Release from Erodible, Poly (N-isopropylacrylamide)-Phospholipid Composites

Erodible, gel-like, polymer-lipid composites were prepared by employing a ther mally reversible polymer, poly( N-isopropylacrylamide) (polyNIPA Am) that has a lower critical solution temperature (LCST). Composites were synthesized by dissolving N-hydroxysuccinimidyl active-ester-group activated polyNIPAAm and lipids including dioleoylphosphatidylethanolamine, dioleoylphosphatidylcholine, and cholesterol in chloroform; hydrating with an aqueous drug solu tion ; and then sonicating the aqueous mixture to a temperature above the LCST of polyNIPAAm. Insulin was suspended in the aqueous solution and was then incorporated within the polymer-lipid composites during formation of the composites. These composites erode away in aqueous solution, gradually releasing the insulin. Increasing frequency of phospholipid (PL) along the polyNIPAAm chain decreases the rates of erosion and drug release The freeze-dried composite has a faster ero sion rate and drug release rate than air-dried composite. The composite eroded and released insulin at temperatures both below and above the LCST of polyNIPAAm. As expected, the composite ero sion and insulin release rates were slower at temperatures above the LCST of polyNIPAAm. The polymer-lipid composites could be useful for topical delivery of protein drugs such as in the eye, nose, mouth, or vagina.