Poly(styrene)-b-poly(DL-lactide) copolymer-based nanoparticles for anticancer drug delivery

Int J Nanomedicine. 2014 Jun 3:9:2803-13. doi: 10.2147/IJN.S62806. eCollection 2014.

Abstract

Poly(styrene)-b-poly(DL-lactide) (PS-PDLLA) copolymer-based nanoparticles (NPs) of a narrow size distribution, negative zeta potential, and spherical shape were fabricated for the delivery of docetaxel (DCT). The particle size was consistently maintained in serum for 24 hours and a sustained drug release pattern was observed for 10 days in the tested formulations. The cytotoxicity of the developed blank NPs was negligible in prostate cancer (PC-3) cells. Cellular uptake and distribution of the constructed NPs containing a hydrophobic fluorescent dye was monitored by confocal laser scanning microscopy (CLSM) for 24 hours. Anti-tumor efficacy of the PS-PDLLA/DCT NPs in PC-3 cells was significantly more potent than that of the group treated with commercially available DCT, Taxotere (P<0.05). Blood biochemistry tests showed that no serious toxicity was observed with the blank NPs in the liver and kidney. In a pharmacokinetic study of DCT in rats, in vivo clearance of PS-PDLLA/DCT NPs decreased while the half-life in blood increased compared to the Taxotere-treated group (P<0.05). The PS-PDLLA NPs are expected to be a biocompatible and efficient nano-delivery system for anticancer drugs.

Keywords: docetaxel; prolonged blood circulation; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / toxicity
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Diffusion
  • Docetaxel
  • Humans
  • Male
  • Nanocapsules / administration & dosage
  • Nanocapsules / chemistry*
  • Nanocapsules / toxicity
  • Particle Size
  • Polyesters / chemistry*
  • Polyesters / toxicity
  • Polystyrenes / chemistry*
  • Polystyrenes / toxicity
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Taxoids / administration & dosage*
  • Taxoids / pharmacokinetics
  • Taxoids / toxicity
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Nanocapsules
  • Polyesters
  • Polystyrenes
  • Taxoids
  • Docetaxel
  • poly(lactide)