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Respirable PLGA microspheres containing rifampicin for the treatment of tuberculosis: screening in an infectious

S Suarez1, P O'Hara, M Kazantseva

  • 1School of Pharmacy, University of North Carolina, Chapel Hill 27599, USA.

Pharmaceutical Research
|October 31, 2001
PubMed
Abstract

Insights

Targeted delivery of rifampicin-loaded microspheres (R-PLGA) to lung macrophages shows promise for treating tuberculosis. This method significantly reduced bacteria, inflammation, and lung damage in a guinea pig model.

Area of Science:

  • Pulmonary Medicine
  • Pharmacology
  • Infectious Diseases

Background:

  • Tuberculosis (TB) is caused by Mycobacterium tuberculosis (MTB), which primarily infects alveolar macrophages.
  • Targeted drug delivery to infected cells is a potential strategy to improve pulmonary tuberculosis therapy.
  • Rifampicin is a key antibiotic for TB treatment.

Purpose of the Study:

  • To evaluate the efficacy of rifampicin-loaded poly(lactide-co-glycolide) microspheres (R-PLGA) delivered via insufflation or nebulization for pulmonary TB.
  • To assess the antimicrobial effect and impact on lung pathology in a guinea pig model.

Main Methods:

  • Guinea pigs were infected with Mycobacterium tuberculosis (MTB) via aerosol exposure.
  • Rifampicin alone (RIF), R-PLGA, or PLGA microparticles were administered by insufflation or nebulization 24 hours before infection.
  • Lung and spleen tissues were analyzed for bacterial load, inflammation, and histopathological damage 28 days post-infection.

Main Results:

  • Insufflated R-PLGA demonstrated a dose-dependent reduction in lung bacterial burden.
  • R-PLGA treatment resulted in significantly fewer viable bacteria, reduced inflammation, and less lung damage compared to controls.
  • Nebulized R-PLGA also showed potential in reducing bacterial load and lung pathology.

Conclusions:

  • Rifampicin-loaded microspheres delivered directly to the lungs show significant potential for treating pulmonary tuberculosis.
  • Insufflation and nebulization are viable delivery methods for R-PLGA in a preclinical model.
  • Targeted delivery of R-PLGA may effectively impact early-stage pulmonary TB development.

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