Inhalation delivery of Telmisartan enhances intratumoral distribution of nanoparticles in lung cancer models

J Control Release. 2013 Nov 28;172(1):86-95. doi: 10.1016/j.jconrel.2013.06.036. Epub 2013 Jul 7.


The purpose of the present study was to evaluate the effect of Telmisartan (Tel) and Losartan (Los) on nanoparticle intratumoral distribution and anticancer effects in lung cancer. A549 lung tumor cells were orthotopically and metastatically administered to Nu/nu mice. Fluorescent polystyrene nanoparticles (FPNPs, size ~200 nm) beads were used to study their intratumoral distribution after Tel and Los treatments. Animals were administered with FPNPs and after 2h, FPNPs intratumoral distribution was studied by fluorescent microscopy. Tel (~1.12 mg/kg) and Los (~4.5mg/kg) were administered by inhalation delivery at alternative days for 4 weeks to tumor bearing animals. Collagen-1, transforming growth factor beta 1 (TGF-β1), cleaved caspase-3, Vimentin and E-Cadherin expressions were studied by western blotting. To correlate the AT1 receptor blockage to anticancer effects, VEGF levels and microvessel densities (MVD) were quantified. Los and Tel treated group resulted in the 5.33 and 14.33 fold increase respectively in the FPNPs intratumoral distribution as compared to the controls. Tel treatment attenuated 2.23 and 1.70 fold Collagen 1 expression compared to untreated control and Los groups, respectively. Further, in Tel and Los treated groups, the TGF-β1 active levels were significantly (p<0.05) decreased. Tel (at four times less dose) was 1.89 and 1.92 fold superior in anticancer activity to Los respectively in A549 orthotopic and metastatic tumor models (p<0.05) when given by inhalation route. Tel, by virtue of its dual pharmacophoric nature could be an ideal candidate for combination therapy to improve the nanoparticle intratumoral distribution and anticancer effects.

Keywords: Collagen; Inhalation; Intratumoral Distribution; Nanotherapeutics; Telmisartan.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Inhalation
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use
  • Benzimidazoles / administration & dosage*
  • Benzimidazoles / pharmacokinetics
  • Benzimidazoles / therapeutic use
  • Benzoates / administration & dosage*
  • Benzoates / pharmacokinetics
  • Benzoates / therapeutic use
  • Cell Line, Tumor
  • Collagen / analysis
  • Female
  • Humans
  • Losartan / administration & dosage*
  • Losartan / pharmacokinetics
  • Losartan / therapeutic use
  • Lung / drug effects
  • Lung / pathology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Mice
  • Nanoparticles / analysis*
  • Telmisartan


  • Antineoplastic Agents
  • Benzimidazoles
  • Benzoates
  • Collagen
  • Losartan
  • Telmisartan