Improving the targeting and therapeutic efficacy of anastrazole for the control of breast cancer: In vitro and in vivo characterization

Int J Pharm. 2024 Nov 15:665:124684. doi: 10.1016/j.ijpharm.2024.124684. Epub 2024 Sep 11.

Abstract

Anastrazole (ASZ) is an effective aromatase inhibitor that is used for breast cancer treatment. Nevertheless, ASZ's effectiveness is diminished due to its low water solubility, unregulated release, absence of targeting, and inadequate patient compliance. The goal of the research was to create a hydrogel formulation of ASZ-loaded invasomes (ALI) to enhance the solubility, permeability, targeting, and efficacy of ASZ while also sustaining its release for treatment of breast cancer. The optimized ALI formulation was determined to be 3%w/v phospholipid, 0.15%w/v cholesterol, 3%v/v ethanol, and 1 %v/v cineole based on the results of the pre-formulation study. After conducting in vitro characterization of the optimum formulation, it was combined with carbopol for in vivo examination of its anti-tumor efficacy in a rat model of 7, 12-dimethylbenzanthracene. Compared to free ASZ, ALI hydrogel increased its penetration by 10.67 times and prolonged its release by 64.02%. Compared to the control positive group, ALI hydrogel reduced tumor volume by 99.19% and mortality by 10.93%. The anti-tumor effect of the ALI hydrogel was demonstrated by its ability to accumulate more ASZ in tumors and reduce hypercellular tumors. Overall, transdermal ALI hydrogel shows potential as a promising approach for treating breast cancer.

Keywords: 7, 12-Dimethylbenzanthracene; Anastrazole; Breast Cancer; Invasomes; Targeting.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene
  • Anastrozole* / administration & dosage
  • Animals
  • Aromatase Inhibitors / administration & dosage
  • Aromatase Inhibitors / chemistry
  • Aromatase Inhibitors / pharmacokinetics
  • Aromatase Inhibitors / pharmacology
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Cell Line, Tumor
  • Drug Delivery Systems / methods
  • Drug Liberation
  • Female
  • Humans
  • Hydrogels* / chemistry
  • MCF-7 Cells
  • Nitriles / chemistry
  • Rats
  • Solubility
  • Triazoles / administration & dosage
  • Triazoles / chemistry
  • Triazoles / pharmacokinetics
  • Triazoles / pharmacology

Substances

  • Hydrogels
  • Anastrozole
  • 9,10-Dimethyl-1,2-benzanthracene
  • Nitriles
  • Triazoles
  • Aromatase Inhibitors