Nanostructured Lipid Microparticles as Tobramycin Carriers for Pulmonary Drug Delivery.

Background/Objectives: Targeted pulmonary delivery of antibiotics offers a favorable approach for the treatment of lower respiratory tract infections (LRTIs) by enhancing local drug concentrations while minimizing systemic exposure. This study aimed to develop and characterize fatty acid-based nanostructured lipid carrier (NLC) microparticles, including tobramycin-loaded formulations, and assess their potential application as carriers for pulmonary drug delivery. Methods: Tobramycin-loaded NLC microparticles were prepared using a hot emulsification method, with lauric acid as the solid lipid and oleic acid as the liquid lipid. The obtained formulations were characterized in terms of morphology, particle size distribution, zeta potential, thermal properties, encapsulation efficiency, drug-release behavior, aerodynamic properties, and powder flowability. Antibacterial activity was evaluated against S. aureus and P. aeruginosa, while cytocompatibility was assessed using BEAS-2B human-lung epithelial cells. Results: The developed microparticles exhibited spherical morphology, with particle characteristics influenced by lipid composition. Incorporation of oleic acid increased tobramycin encapsulation efficiency, reaching approximately 75% at liquid lipid concentrations of 5-15%. Theoretical aerodynamic diameters remained within the respirable range, and increasing oleic acid content improved powder flowability. Drug-release behavior was strongly dependent on lipid composition, with the optimized formulation providing prolonged tobramycin release over 72 h. All formulations preserved antibacterial activity against S. aureus and P. aeruginosa and demonstrated good cytocompatibility with BEAS-2B cells. Conclusions: Fatty acid-based nanostructured lipid microparticles represent a promising active carrier platform for the pulmonary delivery of tobramycin. The developed system demonstrated efficient drug encapsulation, satisfactory particle characteristics, controlled drug release, preserved antibacterial activity, and good biocompatibility, making them a suitable component of dry powders for inhalation (DPI).