title: Linolenic acid-modified PEG-PCL micelles for curcumin delivery.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Engineering, School of Biological Science and Technology, University of Jinan, 336 Nanxinzhuang Xilu, Jinan, Shandong Province 250022, PR China.
authors.forename: Zhimei
authors.initials: Z
authors.lastname: Song
authors.affiliation: School of Medicine and Life Sciences, University of Jinan, 336 Nanxinzhuang Xilu, Jinan, Shandong Province 250022, PR China; Shandong Academy of Medical Sciences, 18877 Jingshi Road, Jinan, Shandong Province 250062, PR China.
authors.forename: Wenxia
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Pharmaceutical Engineering, School of Biological Science and Technology, University of Jinan, 336 Nanxinzhuang Xilu, Jinan, Shandong Province 250022, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Engineering, School of Biological Science and Technology, University of Jinan, 336 Nanxinzhuang Xilu, Jinan, Shandong Province 250022, PR China.
authors.forename: Fengying
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutical Engineering, School of Biological Science and Technology, University of Jinan, 336 Nanxinzhuang Xilu, Jinan, Shandong Province 250022, PR China. Electronic address: runliangfeng@126.com.
authors.forename: Runliang
authors.initials: R
authors.lastname: Feng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D004912:Erythrocytes / Q000187:drug effects; D005026:Ethylene Glycols / Q000737:chemistry*; D006367:HeLa Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008297:Male; D008823:Micelles; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011817:Rabbits; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D014018:Tissue Distribution; D017962:alpha-Linolenic Acid / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005026:Ethylene Glycols; D008823:Micelles; D011091:Polyesters; C476300:poly(epsilon-caprolactone)-b-poly(ethylene glycol); D017962:alpha-Linolenic Acid; D003474:Curcumin
keywords: Curcumin; Linolenic acid; Micelles; PEG-PCL