Temperature/pH-Triggered PNIPAM-Based Smart Nanogel System Loaded With Anastrozole Delivery for Application in Cancer Chemotherapy.

Thermo and pH-responsive poly-N-isopropylacrylamide (PNIPAM) polymer has gained interest due to microenvironment targeting potential toward cancer cells. Its exceptional potential of the phase transition at body temperature (37°C) makes it biologically relevant for drug delivery and biosensing. The optimum drug loading and particle size with controlled release at a specific site are essential for critical process parameters (CPP). This study investigates the formulation optimization anastrozole (ANST)-loaded PNIPAM nanoparticle (NPs) prepared by solvent evaporation method for pH- and thermo-responsive drug delivery. Box-Behnken design (BBD) was implemented to observe the effect of selected process parameters on quality attributes product including particle size 110.15 nm, zeta potential - 11.02 mV, PDI 0.175, and drug loading 8.35% (DL). The statistical data was found to fit in the quadratic model and p value is less than 0.005. The thermo-responsive behavior of PNIPAM is evaluated on DLS and UV-Visible spectroscopy at elevated temperature to 60°C that has shown increment in turbidity showed aggregation of the nanoparticles. The TEM and AFM revealed the spherical and smooth surface ANST-PNIPAM NPs. The formulation showed the controlled release of ANST for 48 h at pH 7.4 and triggered release at simulated tumor microenvironment pH 5.0. The in vitro cytotoxicity of the formulation is higher than free ANST and shown dose-dependent cell viability. The higher cell uptake was observed by NPs after 12-h incubation in MCF-7 cell lines using confocal microscopy. Apoptotic evaluation of ANST-PNIPAM NPs exhibited 22.67% in comparison to free ANST where 6% was analyzed on the flow cytometer.