Novel amphiphilic folic acid-cholesterol-chitosan micelles for paclitaxel delivery

Oncotarget. 2017 Jan 10;8(2):3315-3326. doi: 10.18632/oncotarget.13757.

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.

Keywords: chitosan; cholesterol; folate acid; micelle; paclitaxel.

MeSH terms

  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chitosan* / chemistry
  • Cholesterol* / chemistry
  • Drug Liberation
  • Folic Acid* / chemistry
  • Humans
  • Hydrogen-Ion Concentration
  • Micelles*
  • Paclitaxel / administration & dosage*
  • Paclitaxel / chemistry
  • Particle Size
  • Proton Magnetic Resonance Spectroscopy

Substances

  • Antineoplastic Agents, Phytogenic
  • Micelles
  • Chitosan
  • Folic Acid
  • Cholesterol
  • Paclitaxel