Pegylated multifunctional pH-responsive targeted polymeric micelles for ovarian cancer therapy: synthesis, characterization and pharmacokinetic study

Abstract

DTX-loaded folate targeted micelles (DTX/FA-PEG-HEP-CA-TOC) were prepared using a dialysis method and the impact of various processing variables were evaluated on micelle properties. In vitro cytotoxicity and in vivo pharmacokinetics of the optimized formulation were evaluated.

DTX/FA-PEG-HEP-CA-TOC exhibited average particle size of 90–185 nm with high entrapment efficiency (53–93%) and pH-dependent drug release behavior. DTX/FA-PEG-HEP-CA-TOC micelles exhibited higher toxicity against SKOV3 cells than DTX/HEP-CA-TOC micelles and free DTX. Significant increase in the T_1/2 β, AUC and MRT and decrease in V_d as well as CL values was observed in DTX/FA-PEG-HEP-CA-TOC micelle treated group compared to free DTX treated group.

Graphical Abstract

Keywords:

• Docetaxel
• heparin
• ovarian cancer
• pH-sensitive
• pharmacokinetics
• targeted polymeric micelle

Disclosure statement

The authors report no conflicts of interest in this work. The authors alone are responsible for the content and writing of the article.

Additional information

Funding

This work was supported by Vice Chancellery of Isfahan University of Medical Sciences [grant number: 396507] and the Iran National Science Foundation [INSF, grant number: 96014296].