Rifapentine-proliposomes for inhalation: in vitro and in vivo toxicity.

Autor:	Patil-Gadhe AA; Department of Pharmaceutics, Bharati Vidyapeeth University, Poona College of Pharmacy, Erandwane, Pune, India ; National Centre for Cell Sciences, University of Pune Campus, Ganeshkhind, Pune, India., Kyadarkunte AY; Department of Pharmaceutics, Bharati Vidyapeeth University, Poona College of Pharmacy, Erandwane, Pune, India ; National Centre for Cell Sciences, University of Pune Campus, Ganeshkhind, Pune, India., Pereira M; Department of Microbiology, National Aids Research Centre, Bhosari, Pune, Maharashtra, India., Jejurikar G; Department of Microbiology, National Aids Research Centre, Bhosari, Pune, Maharashtra, India., Patole MS; National Centre for Cell Sciences, University of Pune Campus, Ganeshkhind, Pune, India., Risbud A; Department of Microbiology, National Aids Research Centre, Bhosari, Pune, Maharashtra, India., Pokharkar VB; Department of Pharmaceutics, Bharati Vidyapeeth University, Poona College of Pharmacy, Erandwane, Pune, India.
Jazyk:	angličtina
Zdroj:	Toxicology international [Toxicol Int] 2014 Sep-Dec; Vol. 21 (3), pp. 275-82.
DOI:	10.4103/0971-6580.155361
Abstrakt:	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.
Databáze:	MEDLINE
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