Linolenic acid-modified PEG-PCL micelles for curcumin delivery.

In this study, a novel linolenic acid-modified poly(ethylene glycol)-b-poly(ϵ-caprolactone) copolymer was prepared through radical addition, ring-opening polymerization, and N-acylation reactions. Its structure was characterized by (1)H NMR and GPC. Micelles were developed by thin-film hydration and used as a delivery system for curcumin with high drug loading capacity of 12.80% and entrapment efficiency of 98.53%. The water solubility of curcumin was increased to 2.05 mg/mL, which was approximately 1.87×10(5) times higher than that of free curcumin. The micelles were spherical shape with an average diameter of 20.8±0.8 nm. X-ray diffraction and FT-IR studies suggested that curcumin existed in the polymeric matrices under π-π conjugation and hydrogen bond interaction with the copolymer. In vitro drug release studies indicated that the curcumin release from linolenic acid-modified copolymer micelles met controlled release, and its release rate was less than that from the linolenic acid-unmodified copolymer micelles. Cytotoxicities against Hela and A-549cells demonstrated that the additional π-π conjugation could affect curcumin's anticancer activity through reducing its release from micelles. Hemolysis test and intravenous irritation test results revealed that the linolenic acid-modified copolymer was safe for intravenous injection. The plasma AUC0-∞ and MRT0-∞ of curcumin-loaded linolenic acid-conjugated poly(ethylene glycol)-b-poly(ϵ-caprolactone) copolymer micelles were 2.75- and 3.49-fold higher than that of control solution, respectively. The CLz was also decreased by 2.75-fold. So, this linolenic acid-modified copolymer might be a carrier candidate for curcumin delivery.