Chitosan stabilized camptothecin nanoemulsions: Development, evaluation and biodistribution in preclinical breast cancer animal mode

Int J Biol Macromol. 2017 Nov;104(Pt B):1846-1852. doi: 10.1016/j.ijbiomac.2017.05.127. Epub 2017 May 22.

Abstract

Clinical use of camptothecin (CPT) is hindered due to its poor water and oil solubility, active lactone ring instability and non-targeted toxicity. Recently we reported formulation of camptothecin microemulsions with increased solubility for the improved treatment of breast cancer. In this research chitosan stabilized camptothecin nanoemulsions (CHI-CPT-NEs) were formulated improve the cancer targeting efficiency of CPT. The developed NEs were characterized for their droplet size distribution, stability in plasma and evaluated for in-vitro drug release, in-vivo targeting potential, in-vitro hemolytic potential, cytotoxicity, genotoxicity and in-vivo biodistribution. The CHI-CPT-NEs showed uniform droplet size distribution, extended drug release (61.65±1.57% at 24h), tolerable hemolytic potential (16.4±1.4%), significant cytotoxicity (178±4.3ng/ml) against MCF-7 cancer cells and low DNA damage to lymphocytes. In-vivo biodistribution study conducted in 4T1-breast tumor xenograft BALB/c mice showed that 2495.22±174.66ng/gm of camptothecin was passively targeted to breast cancer by CHI-CPT-NEs compared to the non-stabilized nanoemulsion (1677.58±134.21ng/gm). Thus, passive targeting of developed CHI-CPT-NEs may provide a promising approach for the efficient breast cancer therapy.

Keywords: Breast cancer; Camptothecin nanoemulsion; Chitosan.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Camptothecin / administration & dosage*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chitosan* / chemistry
  • Disease Models, Animal
  • Drug Carriers / chemistry
  • Drug Evaluation, Preclinical
  • Drug Liberation
  • Drug Stability
  • Emulsions
  • Female
  • Humans
  • MCF-7 Cells
  • Mice
  • Nanoparticles* / chemistry
  • Tissue Distribution
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Drug Carriers
  • Emulsions
  • Chitosan
  • Camptothecin