<p>Development of Rifapentine-Loaded PLGA-Based Nanoparticles: In vitro Characterisation and in vivo Study in Mice</p>

Abstract

Background: 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. Methods: 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. Results: The resulting NPs showed suitable and safe physicochemical characteristics and could be taken up by macrophages. RPT-loaded NPs were more effective against Mycobacterium tuberculosis than free RPT. In vivo studies revealed that NPs could improve pharmacokinetic parameters, particularly for RPT/PLGA-PEG NPs. Moreover, both formulations had no toxicity to the organs of mice and could reduce hepatotoxicity. Conclusion: 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.

PEG–PLGA nanoparticles for encapsulating ciprofloxacin

“…These results suggest the possibility of using the antibiotic-loaded nanoparticles as a novel intracellular medicament to provide a clean and sterile environment during the tissue regeneration. Although there are many studies that have evaluated PEG–PLGA nanoparticles in vivo 56 – 58 , additional in vivo studies of CIP-loaded PEG–PLGA NPs should be performed in terms of their toxicity, long-term efficiency, and biological interaction with SCAPs.…”

Recent advances in PLGA micro/nanoparticle delivery systems as novel therapeutic approach for drug-resistant tuberculosis

“…Hence, the ethionamide-based PLGA nanoparticles have great potential for reducing the dosing frequency of ethionamide in treating MDR-TB. PLGAbased nanoparticles could also act as a sustained-release delivery vehicle for rifapentine to prolong drug release, alter pharmacokinetics, increase anti-tuberculosis activity, and reduce toxicity, allowing for low dose and frequency (Liang et al, 2020). Future studies on toxicity studies of drug-loaded nanoparticles and the chemotherapeutic potential of ethionamide-loaded nanoparticles against Mycobacterium tuberculosis (Mtb) in clinics should be performed.…”

Optimization, Characterization and Pharmacokinetic Study of Meso-Tetraphenylporphyrin Metal Complex-Loaded PLGA Nanoparticles

“…The hemolytic activity of Mn-loaded NPs could be explained by their positive surface charge [75,76]. However, MnClTPP-NPs lacked hemolytic activity at concentrations lower than 0.09 mg/mL, demonstrating biocompatibility and potential for application in nanomedicine [77][78][79][80][81]. Thus, MeP-loaded NPs demonstrated good potential for application in drug delivery systems as blood-compatible vehicles.…”