Formulation, characterization and pulmonary deposition of nebulized celecoxib encapsulated nanostructured lipid carriers

Abstract

The aim of the current study was to encapsulate celecoxib (Cxb) in the nanostructured lipid carrier (Cxb-NLC) nanoparticles and evaluate the lung disposition of nanoparticles following nebulization in Balb/c mice. Cxb-NLC nanoparticles were prepared with Cxb, Compritol, Miglyol and sodium taurocholate using high-pressure homogenization. Cxb-NLC nanoparticles were characterized for physical and aerosol properties. In-vitro cytotoxicity studies were performed with A549 cells. The lung deposition and pharmacokinetic parameters of Cxb-NLC and Cxb solution (Cxb-Soln) formulations were determined using the Inexpose™ system and Pari LC star jet nebulizer. The particle size and entrapment efficiency of the Cxb-NLC formulation were 217 ± 20 nm and > 90%, respectively. The Cxb-NLC released the drug in controlled fashion, and in-vitro aerosolization of Cxb-NLC formulation showed an FPF of 75.6 ± 4.6%, MMAD of 1.6 ± 0.13 µm and a GSD of 1.2 ± 0.21. Cxb-NLC showed dose and time dependent cytotoxicity against A549 cells. Nebulization of Cxb-NLC demonstrated 4 fold higher AUC t / D in lung tissues compared to the Cxb-Soln. The systemic clearance of Cxb-NLC was slower (0.93 l/h) compared to the Cxb-Soln (20.03 l/h). Cxb encapsulated NLC were found to be stable and aerodynamic properties were within the respirable limits. Aerosolization of Cxb-NLC improved the Cxb pulmonary bioavailability compared to solution formulation which will potentially lead to better patient compliance with minimal dosing intervals.