title: 9-NC-loaded folate-conjugated polymer micelles as tumor targeted drug delivery system: preparation and evaluation in vitro.
abstract: In this study, folate-conjugated polymer micelles were synthesized by mixing folate-poly(ethylene glycol)-distearoylphosphatidylethanolamine (FA-PEG-DSPE) and methoxy-poly(ethylene glycol)-distearoylphosphatidylethanolamine (MPEG-DSPE) to encapsulate anticancer agent 9-nitro-camptothecin (9-NC). Formulations were characterized by critical micellization concentration (CMC) values of copolymers, micelle particle size, zeta-potential, encapsulation efficiency and drug loading efficiency. The molar ratio of FA-PEG-DSPE and MPEG-DSPE was chosen to avoid the macrophages and at the same time express highly active targeting ability. The targeting ability of folate-conjugated polymer micelles was investigated against three kinds of tumor cell lines (HeLa, SGC7901 and BXPC3). The drug efficacy in vitro of folate-conjugated polymer micelles was evaluated by using the methylthiazoletetrazolium (MTT) method. The results showed that the CMC values of MPEG-DSPE and FA-PEG-DSPE were 0.97 x 10(-5)M and 1.0 x 10(-5)M, respectively. The average size of folate-conjugated micelle was about 21-24 nm and the micelle size distribution of both empty and drug-loaded micelles were rather narrow. The encapsulation efficiency and drug loading efficiency were 97.6% and 4.64%, respectively. The drug-loaded micelles were stable during storage at 4 degrees C for 4 weeks. Micelles maintain the similar size and did not show 9-NC leakage. The best molar ratio of FA-PEG-DSPE and MPEG-DSPE in folate-conjugated micelles was 1:100 which can effectively solubilize 9-NC, avoid the macrophages in vitro and has a higher anti-tumor activity than both drug-loaded MPEG-DSPE micelles and free anticancer agents. The folate-conjugated polymer micelle which can avoid the macrophages is a kind of promising carrier for poorly soluble anticancer agents via folate receptor (FR) that mediated endocytosis to target tumor cells.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Han
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Cao
authors.initials: C
authors.lastname: Xie
authors.forename: Changyou
authors.initials: C
authors.lastname: Zhan
authors.forename: Bing
authors.initials: B
authors.lastname: Gu
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Linglin
authors.initials: L
authors.lastname: Feng
authors.forename: Weiyue
authors.initials: W
authors.lastname: Lu
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005492:Folic Acid / Q000008:administration & dosage* / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D011108:Polymers; D005492:Folic Acid; C079905:rubitecan; D002166:Camptothecin