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Published on: June 8, 2012
The behavior of PLGA microspheres containing rifampicin in alveolar macrophages
T Onoshita1, Y Shimizu, N Yamaya
1Faculty of Pharmaceutical Sciences, Tokyo University of Sciences, Noda, Chiba, Japan.
Abstract:
We have developed a pulmonary drug delivery system for the treatment of tuberculosis using rifampicin (RFP) encapsulated in poly-(lactic-co-glycolic acid) microspheres (RFP-PLGA MS), which is a biocompatible polymer. In this study, the behavior of RFP-PLGA MS and the metabolism of RFP were investigated after their uptake by macrophages using the rat alveolar macrophage cell line, NR8383. The prepared RFP-PLGA MS were spherical with an average diameter of 1.9microm and were taken up effectively by NR8383 cells in an energy-dependent manner. It was shown by fluorescent microscopic studies that the RPF-PLGA MS taken up by the cells were localized in phago-lysosomes and then degraded. Although a small amount of 3-formylrifamycin SV (3-FRSV) was generated by the metabolism of RFP, almost all RFP remained unchanged. It was considered, therefore, that RFP was released into the cytosol with drug potency intact. Based on these results, RFP-PLGA MS will be effective for the delivery of anti-tuberculosis drugs such as RFP, and will be a potentially useful drug delivery tool for pulmonary and possibly other tissues as well.
Insights
This study developed rifampicin-poly(lactic-co-glycolic acid) microspheres for tuberculosis treatment. The drug delivery system effectively released potent rifampicin within macrophages, showing promise for pulmonary drug delivery.
Area of Science:
- Biomedical Engineering
- Pharmacology
- Drug Delivery Systems
Background:
- Tuberculosis (TB) remains a significant global health challenge, necessitating improved drug delivery strategies.
- Pulmonary drug delivery offers targeted treatment for lung infections like TB.
- Poly(lactic-co-glycolic acid) (PLGA) microspheres are a promising biocompatible platform for controlled drug release.
Purpose of the Study:
- To develop and evaluate a novel pulmonary drug delivery system for tuberculosis treatment using rifampicin (RFP) encapsulated in PLGA microspheres (RFP-PLGA MS).
- To investigate the cellular uptake, intracellular fate, and metabolism of RFP-PLGA MS within macrophages.
- To assess the potential of RFP-PLGA MS as an effective drug delivery tool for anti-tuberculosis therapy.
Main Methods:
- Preparation and characterization of RFP-PLGA MS, including size and morphology analysis.
- In vitro evaluation of RFP-PLGA MS uptake by the rat alveolar macrophage cell line (NR8383).
- Fluorescent microscopy to track intracellular localization and degradation of microspheres.
- Analysis of rifampicin metabolism within macrophages.
Main Results:
- RFP-PLGA MS were spherical with an average diameter of 1.9 micrometers.
- NR8383 cells effectively and energy-dependently internalized RFP-PLGA MS.
- Microspheres were localized in phago-lysosomes and subsequently degraded.
- Rifampicin was released into the cytosol with its drug potency largely intact, with minimal metabolism to 3-formylrifamycin SV (3-FRSV).
Conclusions:
- RFP-PLGA MS demonstrate effective cellular uptake and intracellular drug release within macrophages.
- This system shows significant potential for delivering anti-tuberculosis drugs like rifampicin to the lungs.
- RFP-PLGA MS represent a promising drug delivery tool for pulmonary and potentially other tissue-specific therapies.
