Simultaneous Optimization of Cisplatin-Loaded PLGA-mPEG Nanoparticles with Regard to their Size and Drug Encapsulation
Abstract:A central composite experimental design was applied to investigate the effect of five preparative variables on the size and cisplatin encapsulation efficiency of poly(lactide-co-glycolide)-methoxy poly(ethylene glycol) (PLGA-mPEG) nanoparticles. The nanoparticles were prepared by a nano-precipitation process and were characterized with regard to their morphology by scanning electron microscopy, their size by photon correlation spectroscopy and their drug content by atomic absorption spectroscopy respectively. The preparative variables investigated were: solids concentration, aqueous to organic phase volume ratio, temperature, rate of organic phase addition in aqueous phase and agitation. The nanoparticles prepared in this study appeared to be spherical and rather homogeneous in size under the scanning electron microscope. The size and the drug encapsulation of the prepared nanoparticles ranged between 90-180 nm and 0%-40%, respectively. The fitted model could adequately describe the experimental data. The statistical analysis showed that all preparative variables studied, except temperature, affected significantly both the size and the drug loading of nanoparticles. The size was most affected by the agitation whereas the loading was most affected by the phase ratio. Significant interactions between the preparative variables were also observed. The “desirability function” approach was applied to simultaneously optimize the nanoparticles with regard to their size and cisplatin encapsulation. The predictive power of the applied model was more satisfactory in the case of nanoparticles size than with cisplatin encapsulation efficiency. It appears to be feasible to select optimum conditions for the preparation of PLGA-mPEG nanoparticles of cisplatin based on a central composite design and the “desirability function” optimization approach.
Document Type: Research Article
Publication date: May 1, 2008
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