Pulmonary Delivery of Docetaxel and Celecoxib by PLGA Porous Microparticles for Their Synergistic Effects Against Lung Cancer

Background: using a combination of chemotherapeutic agents with novel drug delivery platforms to enhance the anticancer efficacy of the drug and minimizing the side effects, is imperative to lung cancer treatments. Objective: The aim of the present study was to develop, characterize, and optimize porous poly (D, L-lactic-co-glycolic acid) (PLGA) microparticles for simultaneous delivery of docetaxel (DTX) and celecoxib (CXB) through the pulmonary route for lung cancer. Methods: Drug-loaded porous microparticles were prepared by an emulsion solvent evaporation method. The impact of various processing and formulation variables including PLGA amount, dichloromethane volume, homogenization speed, polyvinyl alcohol volume, and concentration, was assessed based on entrapment efficiency, mean release time, particle size, mass median aerodynamic diameter, fine particle fraction, and geometric standard deviation using a twolevel factorial design. An optimized formulation was prepared and evaluated in terms of size and morphology using a scanning electron microscope. Results: FTIR, DSC, and XRD analyses confirmed drug entrapment and revealed no drug-polymer chemical interaction. Cytotoxicity of DTX along with CXB against A549 cells was significantly enhanced compared to DTX and CXB alone and the combination of DTX and CXB showed the greatest synergistic effect at a 1/500 ratio. Conclusion: In conclusion, the results of the present study suggest that encapsulation of DTX and CXB in porous PLGA microspheres with desirable features is feasible and their pulmonary co-administration would be a promising strategy for the effective and less toxic treatment of various lung cancers.