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 1H 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 2.05mg/mL, which was approximately 1.87×105 times higher than that of free curcumin. The micelles were spherical shape with an average diameter of 20.8±0.8nm. 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. [ABSTRACT FROM AUTHOR]