title: Folate-mediated targeted and intracellular delivery of paclitaxel using a novel deoxycholic acid-O-carboxymethylated chitosan-folic acid micelles.
abstract: BACKGROUND
  A critical disadvantage for successful chemotherapy with paclitaxel (PTX) is its nontargeting nature to cancer cells. Folic acid has been employed as a targeting ligand of various anticancer agents to increase their cellular uptake within target cells since the folate receptor is overexpressed on the surface of such tumor cells. In this study, a novel biodegradable deoxycholic acid-O-carboxymethylated chitosan-folic acid conjugate (DOMC-FA) was used to form micelles for encapsulating the anticancer drug PTX.
  
  
  RESULTS
  The drug-loading efficiency, encapsulation efficiency, in vitro drug release and physicochemical properties of PTX-loaded micelles were investigated in detail. In vitro cell culture studies were carried out in MCF-7 cells, a human breast carcinoma cell line, with folate receptor overexpressed on its surface. An increased level of uptake of folate-conjugated micelles compared to plain micelles in MCF-7 cells was observed, and the enhanced uptake of folate-micelles mainly on account of the effective process of folate receptor-mediated endocytosis. The MTT assay, morphological changes, and apoptosis test implied that the folate-conjugated micelles enhanced the cell death by folate-mediated active internalization, and the cytotoxicity of the FA-micellar PTX (DOMC-FA/PTX) to cancer cells was much higher than micelles without folate (DOMC/PTX) or the commercially available injectable preparation of PTX (Taxol).
  
  
  CONCLUSIONS
  Results indicate that the PTX-loaded DOMC-FA micelle is a successful anticancer-targeted drug-delivery system for effective cancer chemotherapy.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan, People's Republic of China.
authors.forename: Feihu
authors.initials: F
authors.lastname: Wang
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Dianrui
authors.initials: D
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Dandan
authors.initials: D
authors.lastname: Zheng
authors.forename: Leilei
authors.initials: L
authors.lastname: Hao
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.forename: Cunxian
authors.initials: C
authors.lastname: Duan
authors.forename: Lejiao
authors.initials: L
authors.lastname: Jia
authors.forename: Guangpu
authors.initials: G
authors.lastname: Liu
mesh_terms: D020341:Absorbable Implants; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002462:Cell Membrane / Q000187:drug effects / Q000473:pathology; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D048271:Chitosan / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D008823:Micelles; D008856:Microscopy, Fluorescence; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D012235:Rhodamines / Q000493:pharmacokinetics; D012995:Solubility; D014407:Tumor Cells, Cultured
chemical_list: D004337:Drug Carriers; D008823:Micelles; D012235:Rhodamines; D048271:Chitosan; D005492:Folic Acid; D017239:Paclitaxel