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Distribution and deposition of respirable PLGA microspheres in lung alveoli

Keiji Hirota1, Tadafumi Kawamoto, Takehisa Nakajima

  • 1Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan.

Colloids and Surfaces. B, Biointerfaces
|February 7, 2013
PubMed

Insights

Respirable microspheres (MS) for tuberculosis treatment effectively deliver drugs to lung macrophages but show rapid drug elimination, limiting efficacy. Further research is needed to optimize drug release and improve tuberculosis treatment outcomes.

Area of Science:

  • Pulmonary drug delivery
  • Tuberculosis treatment
  • Biomaterials science

Background:

  • Pulmonary tuberculosis treatment with microspheres (MS) is expected to be effective.
  • However, the actual efficacy against Mycobacterium tuberculosis in the lungs is lower than anticipated.

Purpose of the Study:

  • To investigate the distribution and accumulation of poly(lactic-co-glycolic) acid (PLGA) MS in rat lungs.
  • To understand the reasons for the reduced efficacy of MS-based antituberculosis drug delivery.

Main Methods:

  • PLGA MS containing fluorescent coumarin 6 or rifampicin (RFP) were delivered via tracheal insufflation in rats.
  • Pulmonary distribution was assessed by microscopy of lung cryosections.
  • Uptake by alveolar macrophages (AMφ) was evaluated using CD68 staining and RFP quantification.

Main Results:

  • Around 50% of fluorescent PLGA MS reached the alveoli and were ingested by AMφ within 24 hours.
  • PLGA MS significantly increased rifampicin uptake by AMφ (10-fold higher than free RFP).
  • A substantial amount of rifampicin was eliminated from the lungs within 6 hours post-insufflation.

Conclusions:

  • PLGA MS are efficiently delivered to rat lung alveoli and macrophages.
  • While MS enhance drug uptake by macrophages, rapid drug elimination limits sustained therapeutic levels.
  • Optimizing drug release kinetics from MS is crucial for improving tuberculosis treatment effectiveness.

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