Computer Optimization of Stealth Biodegradable Polymeric Dual-loaded Nanoparticles for Cancer Therapy Using Central Composite Face-centered Design

摘要

Background: Combination chemotherapy capable of overcoming cancer drugresistance can be facilitated by nanotechnology.Objective: Synthesis, characterization, statistical experimental design, analysis and optimizationof stealth pH-sensitive polymeric nanoparticles suitable as a platform for simultaneousdelivery of paclitaxel and 17-AAG in breast cancer therapy were investigated.Methods: An acetal crosslinker and a poly(?)caprolactone macromonomer were synthesizedand characterized. The statistical experimental design used was the response surfacemethod (RSM). We used the central composite face-centered design (CCF) in three independentfactors and seventeen runs. Nanoparticles were fabricated by dispersion polymerizationtechniques. Response variables evaluated were: particle size, drug loading, encapsulationefficiency, and in vitro availability.Results: Scanning electron micrographs showed the formation of spherical nanoparticles.Computer software was used for the analysis of variance with a 95% confidence level andQ2 (goodness of prediction) to select an appropriate model for each of the responsevariables. Each term in each of the models was tested for the significance of the regressioncoefficients. The computer software optimizer was used for optimization to select factorcombination to minimize particle size, time (h) for maximum release of paclitaxel and17-AAG, to maximize paclitaxel and 17-AAG loading efficiency and to maximizepaclitaxel and 17-AAG encapsulation efficiency.Conclusion: The optimization was successful, as shown by the validation data which liewithin the confidence intervals of predicted values of the response variables. The selectedfactor combination is suitable for the in vivo evaluation of the nanoparticles loaded withpaclitaxel and 17-AAG.