Background: Combination chemotherapy capable of overcoming cancer drug
resistance can be facilitated by nanotechnology.
Objective: Synthesis, characterization, statistical experimental design, analysis and optimization
of stealth pH-sensitive polymeric nanoparticles suitable as a platform for simultaneous
delivery of paclitaxel and 17-AAG in breast cancer therapy were investigated.
Methods: An acetal crosslinker and a poly(ɛ)caprolactone macromonomer were synthesized
and characterized. The statistical experimental design used was the response surface
method (RSM). We used the central composite face-centered design (CCF) in three independent
factors and seventeen runs. Nanoparticles were fabricated by dispersion polymerization
techniques. Response variables evaluated were: particle size, drug loading, encapsulation
efficiency, 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 and
Q2 (goodness of prediction) to select an appropriate model for each of the response
variables. Each term in each of the models was tested for the significance of the regression
coefficients. The computer software optimizer was used for optimization to select factor
combination to minimize particle size, time (h) for maximum release of paclitaxel and
17-AAG, to maximize paclitaxel and 17-AAG loading efficiency and to maximize
paclitaxel and 17-AAG encapsulation efficiency.
Conclusion: The optimization was successful, as shown by the validation data which lie
within the confidence intervals of predicted values of the response variables. The selected
factor combination is suitable for the in vivo evaluation of the nanoparticles loaded with
paclitaxel and 17-AAG.