Rifapentine‑Proliposomes for Inhalation: In Vitro and In Vivo Toxicity


Affiliations

  • Bharati Vidyapeeth University, Department of Pharmaceutics, Poona College of Pharmacy,, Pune, India
  • University of Pune Campus, Ganeshkhind, National Centre for Cell Sciences, Pune, India
  • National Aids Research Centre, Department of Microbiology, Pune, Maharashtra, India
  • National Aids Research Centre, Department of Microbiology, Pune,, Maharashtra, India
  • Bharati Vidyapeeth University, Department of Pharmaceutics, Poona College of Pharmacy, Pune, India

Abstract

Background: Oral therapy for pulmonary tuberculosis (TB) treatment suffers from the limitation of hepatic metabolism leading insufficient concentration of antitubercular (anti‑TB) drugs in alveolar macrophage which harbors Mycobacterium tuberculosis (MTB). Targeted aerosol delivery of antituberculous drug to lung is efficient for treating local lung TB infection. Objective: The present study was aimed to evaluate rifapentine (RPT) loaded proliposomal dry powder for inhalation (RLDPI) for anti‑TBactivity and cytotoxicity in vitro. In vivo toxicity study was also undertaken in Wistar rats to determine safe concentration of RLDPI for administration. Materials and Methods: Anti‑TB activity of developed RLDPI was assessed using drug susceptibility testing (DST) on Mycobacteria growth indicator tube (MGIT) method. in vitro cytotoxicity was performed in A549 cell lines and IC50 values were used to compare the cytotoxicity of formulation with pure RPT. in vivo repeated dose toxicity study was undertaken using Wistar rats at three different doses for 28‑days by intratracheal insufflations method. Results: The results of DST study revealed sensitivity of tubercle bacteria to RLDPI at concentration equivalent to 10 μg/mL of RPT. This study confirmed anti‑TB potential of RPT in spray‑dried RLDPI, though the spray drying method is reported to reduce activity of drugs. Cytotoxicity study in A549 cells demonstrated that RPT when encapsulated in liposomes as RLDPI was safe to cells as compared to pure RPT. In vivo toxicity study revealed that RPT in the form of RLDPI was safe at 1 and 5 mg/kg dose. However, mortality was seen at higher dose (10 mg/kg), possibly because of liver and kidney damage. Conclusion: Thus, these studies demonstrated safety of RLDPI for the treatment of pulmonary TB.

Keywords

A549 cell line, drug susceptibility testing on Mycobacteria growth indicator tube, pulmonary tuberculosis, rifapentine, toxicity

Subject Discipline

Zoology

Full Text:

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