DEVELOPMENT, CHARACTERIZATION, AND IN VITRO EVALUATION OF PLGA 50:50 NANOPARTICLES AGAINST A MYCOBACTERIUM TUBERCULOSIS STRAIN

Rifampicin (RIF) is one of the main drugs used to treat tuberculosis (TB), primarily caused by Mycobacterium tuberculosis (Mtb) and considered one of the world’s deadliest infectious diseases. However, RIF has limitations in solubility and stability, which compromises its therapeutic efficacy. Nanoencapsulation in biodegradable polymers such as PLGA (poly(lactic-co-glycolic acid)) emerges as an alternative capable of overcoming these barriers, potentially promoting greater stability and controlled drug release. Thus, this study aimed to develop and characterize a PLGA nanoformulation containing RIF and to evaluate its in vitro antimycobacterial activity against a drug-susceptible Mtb strain. The nanoformulation was obtained by the single-emulsion method, using RIF as the model drug, PLGA 50:50 as the polymer matrix, and PVA as the stabilizer. It was characterized for mean diameter (Z-Ave), polydispersity index (PdI), zeta potential (ZP), and encapsulation efficiency (EE%) by DLS and UV-VIS, respectively. In vitro antimycobacterial activity was determined against the drug-susceptible Mtb strain H37Ra by microdilution in plates, using resazurin as the indicator solution. The produced nanoparticles (N-PLGA50:50-RIF) showed Z-Ave of 220.9±2.9 nm, PdI of 0.11±0.05, ZP of -15.4±0.3 mV, indicating adequate homogeneity and colloidal stability, and EE% of 18%. In the in vitro antimycobacterial activity assay, N-PLGA50:50-RIF showed an MIC of 0.031 µg/mL, whereas free RIF had an MIC of 0.250 µg/mL, demonstrating an inhibitory potential approximately eight times greater than the free drug. Thus, we can infer that N-PLGA50:50-RIF had suitable physicochemical characteristics and in vitro antimycobacterial activity superior to free RIF, evidencing the development of a nanoformulation with higher efficacy against the Mtb strain H37Ra. These results reinforce the potential of nanoencapsulation as an alternative to improve rifampicin efficacy in tuberculosis treatment.