Spray-dried fucoidan microparticles for pulmonary delivery of antitubercular drugs

Area of Science:

• Pharmacology
• Biomaterials Science
• Respiratory Medicine

Background:

• Pulmonary tuberculosis is the most common form, necessitating targeted drug delivery to the lungs.
• Alveolar macrophages are key hosts for Mycobacterium tuberculosis, and fucoidan may interact with these cells.
• Reducing systemic drug toxicity is a critical goal in tuberculosis treatment.

Purpose of the Study:

• To develop inhalable fucoidan-based microparticles for pulmonary tuberculosis therapy.
• To encapsulate first-line antitubercular drugs, isoniazid and rifabutin, within these microparticles.
• To evaluate the drug association efficiency, cytotoxicity, and aerodynamic properties of the microparticles.

Main Methods:

• Fucoidan was used as a matrix to create inhalable microparticles.
• Isoniazid and rifabutin were loaded into the fucoidan microparticles.
• Association efficiencies were determined for both drugs.
• Cytotoxicity was assessed using lung epithelial cells (A549) and macrophage-like cells (THP-1).
• Aerodynamic properties, including Mass Median Aerodynamic Diameter (MMAD), were measured.

Main Results:

• High association efficiencies were achieved for isoniazid (95%) and rifabutin (81%).
• Microparticles showed no significant cytotoxicity on lung epithelial cells (A549).
• Rifabutin-loaded microparticles exhibited some toxicity on THP-1 cells at the highest concentration (1 mg/mL).
• The microparticles demonstrated favorable aerodynamic properties (MMAD 2.0-3.8 µm) for deep lung delivery.

Conclusions:

• Inhalable fucoidan microparticles loaded with antitubercular drugs are feasible for pulmonary tuberculosis therapy.
• The microparticles possess suitable characteristics for targeted delivery to the lungs.
• Further investigation into drug release and in vivo efficacy is warranted, particularly concerning rifabutin's macrophage toxicity.