Tumor stromal disrupting agent enhances the anticancer efficacy of docetaxel loaded PEGylated liposomes in lung cancer

Nanomedicine (Lond). 2016 Jun;11(11):1377-92. doi: 10.2217/nnm.16.37. Epub 2016 May 12.

Abstract

Aim: Therapeutic efficacy of anticancer nanomedicine is compromised by tumor stromal barriers. The present study deals with the development of docetaxel loaded PEGylated liposomes (DTXPL) and to investigate the effect of tumor stroma disrupting agent, telmisartan, on anticancer efficacy of DTXPL.

Methods: DTXPL was prepared using proprietary modified hydration method. Effect of oral telmisartan treatment on tumor uptake of coumarin-6 liposomes and anticancer efficacy of DTXPL was evaluated in orthotopic xenograft lung tumor bearing mice.

Results: DTXPL (105.7 ± 3.8 nm) showed very high physical stability, negligible hemolysis, 428% enhancement in bioavailability with significantly higher intratumoral uptake. Marked reduction in collagen-I, MMP2/9 and lung tumor weight were observed in DTXPL+telmisartan group.

Conclusion: Combination of DTXPL with telmisartan could significantly enhance clinical outcome in lung cancer.

Keywords: cancer nanomedicine; docetaxel; orthotopic lung cancer; pegylated liposome; solid tumor targeting; tumor fibrosis; tumor stroma.

MeSH terms

  • A549 Cells
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / pharmacology*
  • Benzoates / administration & dosage
  • Benzoates / pharmacology*
  • Coumarins / chemistry
  • Docetaxel
  • Female
  • Heterografts
  • Humans
  • Liposomes
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Nude
  • Particle Size
  • Polyethylene Glycols / chemistry*
  • Rats
  • Rats, Sprague-Dawley
  • Surface Properties
  • Taxoids / administration & dosage
  • Taxoids / pharmacokinetics
  • Taxoids / pharmacology*
  • Telmisartan
  • Thiazoles / chemistry
  • Tumor Burden / drug effects

Substances

  • Antineoplastic Agents
  • Benzimidazoles
  • Benzoates
  • Coumarins
  • Liposomes
  • Taxoids
  • Thiazoles
  • coumarin 6
  • Docetaxel
  • Polyethylene Glycols
  • Telmisartan