title: Rifapentine-proliposomes for inhalation: in vitro and in vivo toxicity.
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.
  
  
  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.
  
  
  CONCLUSIONS
  Thus, these studies demonstrated safety of RLDPI for the treatment of pulmonary TB.
authors.affiliation: 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.
authors.forename: Arpana A
authors.initials: AA
authors.lastname: Patil-Gadhe
authors.affiliation: 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.
authors.forename: Abhay Y
authors.initials: AY
authors.lastname: Kyadarkunte
authors.affiliation: Department of Microbiology, National Aids Research Centre, Bhosari, Pune, Maharashtra, India.
authors.forename: Michael
authors.initials: M
authors.lastname: Pereira
authors.affiliation: Department of Microbiology, National Aids Research Centre, Bhosari, Pune, Maharashtra, India.
authors.forename: Gauri
authors.initials: G
authors.lastname: Jejurikar
authors.affiliation: National Centre for Cell Sciences, University of Pune Campus, Ganeshkhind, Pune, India.
authors.forename: Milind S
authors.initials: MS
authors.lastname: Patole
authors.affiliation: Department of Microbiology, National Aids Research Centre, Bhosari, Pune, Maharashtra, India.
authors.forename: Arun
authors.initials: A
authors.lastname: Risbud
authors.affiliation: Department of Pharmaceutics, Bharati Vidyapeeth University, Poona College of Pharmacy, Erandwane, Pune, India.
authors.forename: Varsha B
authors.initials: VB
authors.lastname: Pokharkar
keywords: A549 cell line; drug susceptibility testing on Mycobacteria growth indicator tube; pulmonary tuberculosis; rifapentine; toxicity