The efficacy of mycolic acid-enhanced PLGA nanoparticles for rifampicin delivery in tuberculosis treatment

Abstract

This study explored the efficacy of nanoparticle-encapsulated rifampicin formulations for treating high Mycobacterium tuberculosis (M. tuberculosis) bacillary loads using a guinea pig model. Two formulations were compared: rifampicin encapsulated in poly(lactic-co-glycolic acid) (PLGA/RIF) and PLGA/RIF coated with mycolic acid (PLGA/RIF/MA), against traditional rifampicin treatment and control groups. Data obtained from this study will guide optimisation for future drug efficacy testing, particularly for targeted TB treatment. The guinea pig model was chosen due to its physiological and immunological similarities to human TB infection. Detailed investigations included clinical monitoring, macropathological and histopathological assessments, and bacterial load quantification to evaluate treatment efficacy, side effects, and overall animal health. Key findings indicated differences in survival rates, clinical signs of TB progression, and bacterial load reduction among the treatment groups. The PLGA/RIF group showed promising results in terms of survival rates and bacterial load reduction, suggesting potential benefits of nanoparticle-encapsulated drug formulations. However, the addition of mycolic acid in the PLGA/RIF/MA formulation did not significantly enhance treatment outcomes compared to PLGA/RIF alone, highlighting the complexity of optimizing nanoparticle formulations for TB treatment and the need for further research. The study also addressed the challenges of achieving statistical significance in animal model research, particularly in pilot studies with limited sample sizes and high variability. It emphasized the need for method refinement to lower variability and increase method repeatability and reproducibility, leading to more statistically powered studies to confirm preliminary findings and fully assess the efficacy of nanoparticle-encapsulated TB treatments. Additionally, the study recommended serological testing for TB biomarkers as a method for early TB detection in animal models, potentially enabling earlier treatment initiation and providing insights into infection dynamics and treatment response. Overall, this study laid the groundwork for further exploration of nanoparticle-based drug delivery systems in TB treatment. It underscores the considerations in designing targeted drug delivery, the challenges and potential of PLGA as a drug carrier, and the scope for innovative approaches to improve TB treatment efficacy and patient outcomes. Future studies are encouraged to build on these findings, refine animal models, and explore novel early diagnostic methods to advance TB research and treatment.