title: Development of a folate-modified curcumin loaded micelle delivery system for cancer targeting.
abstract: Targeted drug delivery system for tumor cells is an appealing platform on enhancing the therapeutic effects and reducing the side effects of the drug. In this study, we developed folate-modified curcumin (Cur) loaded micelles (Cur-FPPs) for cancer chemotherapy. The targeting material, Folate-PEG3000-PLA2000, was synthesized by the amide bond formation reaction. And the Cur loaded micelles were prepared by thin-film hydration method with mPEG2000-PLA2000 (Cur-PPs) or mPEG2000-PLA2000 and Folate-PEG3000-PLA2000 (Cur-FPPs) as carrier. A central composite design (CCD) was used to optimize the formulation, and the optimized Cur-FPPs was prepared with the weight ratio of Folate-PEG3000-PLA2000 and mPEG2000-PLA2000 at 1:9. The average size of the mixed micelles was 70nm, the encapsulating efficiency and drug-loading were 80.73±0.16% and 4.84±0.01%, respectively. Compared with the Cur propylene glycol solution, the in vitro release of Cur from Cur-FPPs showed a sustained manner. Furthermore, the in vitro cytotoxicity and cellular uptake of Cur-FPPs were significantly enhanced towards MCF-7 and HepG2 cells. The pharmacokinetic studies in rats indicated that a 3-fold increase in the half-life was achieved for Cur loaded micelle formulations relative to solubilized Cur. All the results demonstrated that folate-modified Cur micelles could serve as a potential nanocarrier to improve the solubility and anti-cancer activity of Cur.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, 44 Wenhua Xilu, Jinan 250012, China.
authors.forename: Chunfen
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Section of Cadre Health-Care, Affiliated Hospital of Shandong University of TCM, Jinan 250011, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, 44 Wenhua Xilu, Jinan 250012, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Pang
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, 44 Wenhua Xilu, Jinan 250012, China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Xi
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, 44 Wenhua Xilu, Jinan 250012, China. Electronic address: professorgxzhai@126.com.
authors.forename: Guangxi
authors.initials: G
authors.lastname: Zhai
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D005492:Folic Acid / Q000737:chemistry*; D006461:Hemolysis / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D007509:Irritants / Q000494:pharmacology; D019344:Lactic Acid / Q000138:chemical synthesis / Q000737:chemistry; D061986:MCF-7 Cells; D008297:Male; D008823:Micelles; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000188:drug therapy*; D010316:Particle Size; D011091:Polyesters; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D011817:Rabbits; D051381:Rats; D055672:Static Electricity; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D007509:Irritants; D008823:Micelles; D011091:Polyesters; D011108:Polymers; D013501:Surface-Active Agents; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); D005492:Folic Acid; D003474:Curcumin
keywords: Curcumin; Folate; Micelles; mPEG-PLA