Inhaled Solid Lipid Microparticles to target alveolar macrophages for tuberculosis

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Infectious Disease Research

Background:

• Tuberculosis (TB) remains a global health challenge, necessitating novel therapeutic strategies.
• Conventional TB treatments can have limitations in efficacy and patient compliance.
• Targeting alveolar macrophages is a key strategy for effective anti-tubercular therapy.

Purpose of the Study:

• To evaluate Solid Lipid Microparticles (SLM) as a breathable drug delivery system for targeting alveolar macrophages.
• To enhance the effectiveness of conventional tuberculosis (TB) therapy using rifampicin-loaded SLM.
• To assess the potential of SLM for inhaled anti-TB therapy via a Dry Powder Inhaler.

Main Methods:

• Rifampicin-loaded SLM were formulated using stearic acid and sodium taurocholate.
• Characterization included aerodynamic diameter, surface charge, drug loading, and in vitro release studies.
• Biological activity was assessed against Bacillus subtilis, and cytotoxicity/internalization were evaluated in murine macrophages (J774 cell line) using MTT assay, cytofluorimetry, and confocal microscopy.

Main Results:

• SLM possessed an aerodynamic diameter suitable for alveolar deposition.
• The negatively charged surface of SLM promoted macrophage uptake.
• Rifampicin's antimicrobial activity was preserved, with negligible in vitro release, indicating effective drug entrapment.
• SLM demonstrated non-cytotoxicity and efficient internalization by macrophages.

Conclusions:

• Breathable SLM are a promising carrier for inhaled anti-TB therapy.
• The characterized SLM possess features conducive to alveolar macrophage targeting and endocytosis.
• This microparticulate system offers potential for an efficacious inhaled TB therapy delivered via a Dry Powder Inhaler device.