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Updated: Aug 16, 2026
System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis
Published on: April 5, 2017
Effects of pulmonary surfactant system on rifampicin release from rifampicin-loaded PLGA microspheres
Keishiro Tomoda1, Sayaka Kojima, Megumi Kajimoto
1Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki Noda Chiba 278-8510, Japan.
Abstract:
Pulmonary surfactants little affected the release ratio of rifampicin from rifampicin-loaded poly(lactide-co-glycolide) PLGA microspheres. The release ratio of rifampicin was depending on pH of pulmonary surfactant solution, showing that rifampicin-loaded PLGA microspheres have an ideal property to deliver rifampicin into alveolar macrophages inside of which Mycobacterium tuberculosis bacilli reside and to kill them. That is, little amount of rifampicin is released in alveolar lining liquid before the microspheres are phagocytosed by alveolar macrophages, then rifampicin is released in phagosome or cytoplasm, but little amount of rifampicin is released in lysosome of alveolar macrophages after the microspheres are internalized. Pulmonary surfactants also little affected the changes in molecular weight of residual PLGA during its hydrolytic degradation process. From the electrophoretic mobility measurements of PLGA microspheres, it was shown that pulmonary surfactants changed the surface charge density of PLGA microspheres by adsorbing on their surfaces.
Insights
Pulmonary surfactants minimally impact rifampicin release from poly(lactide-co-glycolide) microspheres. This pH-dependent release is ideal for targeting Mycobacterium tuberculosis within alveolar macrophages, enhancing drug delivery and efficacy.
Area of Science:
- Biomedical Engineering
- Drug Delivery Systems
- Pulmonary Medicine
Background:
- Tuberculosis remains a significant global health challenge, necessitating innovative drug delivery strategies.
- Poly(lactide-co-glycolide) (PLGA) microspheres are a promising platform for sustained drug release.
- Pulmonary surfactants play a crucial role in lung physiology and could influence inhaled drug formulations.
Purpose of the Study:
- To investigate the effect of pulmonary surfactants on the release kinetics of rifampicin from PLGA microspheres.
- To evaluate the pH-dependent release profile of rifampicin from PLGA microspheres in simulated lung environments.
- To assess the impact of pulmonary surfactants on the degradation and surface properties of PLGA microspheres.
Main Methods:
- Preparation of rifampicin-loaded PLGA microspheres.
- In vitro release studies of rifampicin in the presence of varying concentrations and pH of pulmonary surfactants.
- Analysis of PLGA molecular weight changes during hydrolytic degradation.
- Electrophoretic mobility measurements to assess surface charge density changes.
Main Results:
- Pulmonary surfactants showed minimal effect on the overall rifampicin release ratio from PLGA microspheres.
- Rifampicin release was significantly influenced by the pH of the pulmonary surfactant solution.
- Pulmonary surfactants did not substantially alter the molecular weight changes of PLGA during degradation.
- Surface adsorption of pulmonary surfactants altered the surface charge density of the PLGA microspheres.
Conclusions:
- Rifampicin-loaded PLGA microspheres exhibit ideal properties for targeted delivery to alveolar macrophages, with pH-dependent release controlling drug availability.
- The microspheres facilitate intracellular drug release within macrophages, enhancing efficacy against Mycobacterium tuberculosis.
- Pulmonary surfactants minimally affect microsphere integrity and drug release, suggesting compatibility with pulmonary administration routes.
