Microencapsulated Solid Lipid Nanoparticles as a Hybrid Platform for Pulmonary Antibiotic Delivery

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery
• Nanotechnology

Background:

• Tuberculosis remains a major global health challenge requiring innovative treatment strategies.
• Pulmonary drug delivery offers potential for targeted lung treatment and improved efficacy.
• Solid lipid nanoparticles (SLN) are a promising platform for encapsulating drugs like rifabutin (RFB).

Purpose of the Study:

• To develop solvent- and sonication-free solid lipid nanoparticles (SLN) loaded with rifabutin (RFB).
• To microencapsulate RFB-loaded SLN into microspheres for effective pulmonary administration.
• To evaluate the physicochemical properties, in vitro aerosolization, and in vivo efficacy of the developed formulation.

Main Methods:

• Solvent- and sonication-free method for SLN preparation.
• Spray-drying technique for microencapsulation of SLN into microspheres using mannitol and trehalose.
• Confocal microscopy, aerodynamic diameter assessment, twin-impinger studies for characterization.
• Isothermal titration calorimetry for excipient-SLN interaction analysis.
• In vivo biodistribution and antimycobacterial activity assays in a murine tuberculosis model.

Main Results:

• Spherical microspheres with homogeneously distributed SLN were successfully prepared.
• Optimal aerodynamic properties for alveolar deposition were achieved.
• In vitro studies confirmed deep lung delivery potential.
• SLN were readily recovered upon microsphere dissolution, retaining properties.
• In vivo studies showed effective biodistribution and enhanced antimycobacterial activity against M. tuberculosis.

Conclusions:

• Microencapsulation of RFB-loaded SLN is a viable strategy for pulmonary delivery.
• The formulation demonstrates potential for improved tuberculosis treatment.
• This approach offers a promising alternative for delivering antimycobacterial agents to the lungs.