title: Novel amphiphilic folic acid-cholesterol-chitosan micelles for paclitaxel delivery.
abstract: In order to decrease the toxicity of paclitaxel (PTX) and increase the efficiency, we developed an amphiphilic PTX injection system using a biodegradable and biocompatible polymer synthesized by folic acid, cholesterol, and chitosan (FACC). This FACC-based polymer had a low critical concentration (64.13μg/ml) and could self-assemble in aqueous condition to form nanoscale micelles. The particle sizes of FACC-PTX micelles were 253.2±0.56 nm, the encapsulation efficiency and loading capacity of these FACC-PTX micelles were 65.1±0.23% and 9.1±0.16%, respectively. The cumulative release rate was about 85% at pH 5.0 which was higher than that at pH 7.4 (76%). This pH-dependent release behavior was highly suggesting that PTX release from FACC-PTX micelles might be higher in a weak acidic tumor microenvironment and lower toxic for normal cells. The anti-cancer effectiveness of FACC-PTX micelles was investigated by in vitro cytotoxicity and targeting study. The results revealed that FACC micelles have non-toxic on cells as evidenced by high cell viability found (86% to 100%) in the cells cultured with various concentrations of FACC micelles (1 to 500 μg/ml). Targeting study indicated that the cytotoxic efficacy of FACC-PTX micelles was significantly higher than that with Taxol® in the Hela cells (folate receptor-positive cells). These findings indicated that the anticancer efficiency of PTX can be enhanced by adding some cancer cell positive receptor into drug carrier and the FACC micelle was a potential tumor targeting carrier for PXT delivery.
authors.affiliation: Department of Pharmacy, The Second Affiliated Hospital of Dalian Medical University, Liaoning, Dalian 116027, China.
authors.forename: Li-Chun
authors.initials: LC
authors.lastname: Cheng
authors.affiliation: Department of Pharmacy, The Second Affiliated Hospital of Dalian Medical University, Liaoning, Dalian 116027, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Pharmacy, The Second Affiliated Hospital of Dalian Medical University, Liaoning, Dalian 116027, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Pharmacy, The Second Affiliated Hospital of Dalian Medical University, Liaoning, Dalian 116027, China.
authors.forename: Lu-Lu
authors.initials: LL
authors.lastname: Qiu
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA 02144, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, The Second Affiliated Hospital of Dalian Medical University, Liaoning, Dalian 116027, China.
authors.forename: Hui-Yi
authors.initials: HY
authors.lastname: Lu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry; D065546:Drug Liberation; D005492:Folic Acid / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D048271:Chitosan; D005492:Folic Acid; D002784:Cholesterol; D017239:Paclitaxel
keywords: chitosan; cholesterol; folate acid; micelle; paclitaxel