Matryoshka-type gastro-resistant microparticles for the oral treatment of Mycobacterium tuberculosis

Vanesa Andreu1, Ane Larrea1,2, Pablo Rodriguez-Fernandez3,4,5,6

  • 1Department of Chemical Engineering. Aragon Institute of Nanoscience (INA), University of Zaragoza, Campus Río Ebro-Edificio I+D, C/Poeta Mariano Esquillor S/N, Zaragoza 50018, Spain.

Abstract

Insights

New Matryoshka-type microparticles protect rifampicin from stomach acid and effectively eliminate Mycobacterium tuberculosis in vitro. These antibiotic nanoparticles offer sustained release and improved efficacy against tuberculosis.

Area of Science:

  • Pharmaceutical Sciences
  • Biotechnology
  • Materials Science

Background:

  • Tuberculosis (TB) remains a significant global health challenge, necessitating novel drug delivery systems.
  • Current treatments for TB can be limited by drug degradation and suboptimal release kinetics.
  • Poly lactic-co-glycolic acid (PLGA) nanoparticles (NP) offer a promising platform for drug delivery, but require protection from harsh physiological conditions.

Purpose of the Study:

  • To develop Matryoshka-type gastroresistant microparticles encapsulating antibiotic-loaded PLGA nanoparticles.
  • To enhance the stability and efficacy of rifampicin against Mycobacterium tuberculosis.
  • To investigate the drug release profile and intestinal barrier penetration of the novel microparticle system.

Main Methods:

  • Synthesis of PLGA nanoparticles loaded with the antibiotic rifampicin using emulsification and evaporation techniques.
  • Development of a methacrylic acid-ethyl acrylate-based coating for gastroresistance.
  • Evaluation of NP stability under simulated gastric conditions and drug release under simulated intestinal conditions.
  • Assessment of antitubercular activity against Mycobacterium tuberculosis in infected macrophages and in vitro intestinal barrier models.

Main Results:

  • The microparticle coating successfully protected rifampicin-loaded PLGA NPs from degradation in simulated gastric conditions.
  • Sustained release of rifampicin was achieved under simulated intestinal conditions.
  • Encapsulation did not compromise the antitubercular activity of rifampicin.
  • The developed NPs demonstrated superior efficacy in eliminating M. tuberculosis compared to free rifampicin in infected macrophages.
  • The antibiotic-loaded PLGA-NPs exhibited the ability to cross an in vitro model of the intestinal barrier.

Conclusions:

  • Matryoshka-type gastroresistant microparticles provide effective protection for antibiotic-loaded PLGA NPs against gastric degradation.
  • The novel system enables sustained antibiotic release and enhanced efficacy against Mycobacterium tuberculosis.
  • These findings suggest a promising new strategy for oral delivery of anti-TB drugs, improving treatment outcomes.

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