Formulation and optimization of celecoxib-loaded PLGA nanoparticles by the Taguchi design and their in vitro cytotoxicity for lung cancer therapy

Abstract

The objective of the present study was to develop, evaluate and optimize a polymeric nanoparticle (NP) system containing Cxb for pulmonary delivery of Cxb in the treatment of lung cancer. NPs were prepared by the emulsion solvent diffusion and evaporation method using poly(D, L lactideglycolide) (PLGA). The size of NPs ranged from 153 to 192nm and was affected by PLGA content, surfactant concentration and organic phase volume. Zeta potential of NPs (-4.5 to -8.6 mV) was more affected by PLGA content and organic phase volume. PLGA content was also the most effective factor on the entrapment efficiency and release rate of Cxb from NPs. The optimum formulation which obtained with 5mg Cxb, 25mg PLGA, 0.5 surfactant, 2.5 organic volume and 15 000 rpm showed release of Cxb within 30 h. The optimized formulation co-spray dried with lactose (hybrid microparticles) displayed desirable fine particle fraction, mass medium aerodynamic diameter, geometric standard deviation of 70.3, 1.46 and 3.38, respectively. Our results provide evidence for the potential of PLGA NPs for delivery of Cxb through inhalation as means to alleviate the cardiovascular risk of Cxb administration.