rifapentine and Hemolysis

Tuberculosis (TB) is a leading cause of death amongst infectious diseases. The poor response to antitubercular agents necessitates the long-term use of high drug doses, resulting in low patient compliance, which is the main reason for chemotherapy failure and contributes to the development of multidrug-resistant TB. Patient non-compliance has been a major obstacle in the successful management of TB. The aim of this work was to develop and characterise rifapentine (RPT)-loaded PLGA-based nanoparticles (NPs) for reducing dosing frequency.. RPT-loaded PLGA and PLGA-PEG NPs were prepared using premix membrane homogenisation combined with solvent evaporation method. The resulting NPs were characterised in terms of physicochemical characteristics, toxicity, cellular uptake and antitubercular activity. NPs were further evaluated for pharmacokinetic and biodistribution studies in mice.. The application of PLGA-based NPs as sustained-release delivery vehicles for RPT could prolong drug release, modify pharmacokinetics, increase antitubercular activity and diminish toxicity, thereby allowing low dosage and frequency.

Topics: Administration, Oral; Animals; Antitubercular Agents; Drug Carriers; Drug Delivery Systems; Drug Liberation; Hemolysis; Humans; Macrophages; Male; Mice, Inbred BALB C; Mycobacterium tuberculosis; Nanoparticles; Particle Size; Polyesters; Polyethylene Glycols; Prostaglandins A; Rifampin; Tissue Distribution