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Inhalable Chitosan Microparticles: A Spray-Drying Approach for Enhanced Pulmonary Delivery of Rifampicin.

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Spray-dried microparticles efficiently delivered rifampicin to the lungs for tuberculosis treatment. These optimized microparticles demonstrated sustained drug release and enhanced lung retention compared to oral tablets.

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Area of Science:

  • Pharmaceutical Sciences
  • Drug Delivery Systems
  • Pulmonary Medicine

Background:

  • Tuberculosis (TB) treatment requires effective drug delivery to lung tissues.
  • Targeting alveolar macrophages can improve anti-TB efficacy.
  • Developing advanced drug carriers like microparticles is crucial for localized lung delivery.

Purpose of the Study:

  • To develop and optimize spray-dried chitosan microparticles for enhanced rifampicin payload and targeted delivery to alveolar macrophages.
  • To evaluate the physicochemical, aerodynamic, and pharmacokinetic properties of rifampicin-loaded microparticles.
  • To compare the efficacy of microparticle administration with conventional oral rifampicin tablets in a rat model.

Main Methods:

  • Spray drying technique was employed to formulate rifampicin-loaded chitosan microparticles.
  • Optimization of formulation parameters including feed rate, chitosan concentration, and surfactant addition.
  • Characterization involved particle size analysis, morphology (SEM), drug content, drug release studies (in vitro), aerodynamic performance, FTIR, and XRD analysis.
  • Pharmacokinetic studies were conducted in rats following oral and intratracheal administration.

Main Results:

  • Optimized microparticles (2-6 μm) with high rifampicin loading (>60% association efficiency) and good yield (23-51%) were successfully produced.
  • Sustained rifampicin release (>95%) via anomalous non-Fickian diffusion was observed.
  • Excellent aerodynamic properties were achieved, with an inhaled fraction of 69% and fine particle fraction (FPF) of 51.51% for particles ≤3 μm.
  • Intratracheal administration resulted in significantly lower AUC (80.845 ± 9.42 μg/mL·h) compared to oral tablets (140.468 ± 12.53 μg/mL·h), indicating enhanced lung retention.

Conclusions:

  • Spray-dried chitosan microparticles represent a promising platform for targeted pulmonary delivery of rifampicin.
  • The optimized microparticles demonstrated superior pharmacokinetic profile and lung retention, suggesting potential for improved tuberculosis treatment.
  • Further investigation into these microparticles could lead to novel strategies for managing lung infections.