TPGS-PLA nanomicelles for targeting lung cancer; synthesis, characterization, and in vitro antitumor efficacy

Combination therapy is a significant approach to enhance antitumor efficacy. Several mechanisms like tumor progression and neo angiogenesis can be targeted together via combination therapy to achieve successful anti-cancer effect. The proposed study involves preparation and optimization of antitumor drugs Palbociclib (PAL) and Regorafenib (REG) encapsulated in D-alpha-Tocopheryl Polyethylene Glycol Succinate (TPGS) Poly lactic acid (PLA) nanomicelles to treat lung cancer. TPGS-PLA nanomicelles were fabricated with thin film hydration method. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and H-1 nuclear magnetic resonance ((HNMR)-H-1) was performed to confirm polymerization of TPGS-PLA. PAL and REG loaded TPGS-PLA nanomicelles (PAL-REG-TPGS-PLAM) components were optimized using Box Behnken design. Particle size (PS), polydispersity index (PDI) and zeta potential (ZP) were evaluated using zetasizer followed by inves-tigating the morphology of nanomicelles via scanning electron microscopy (SEM). Moreover, in vitro release of PAL-REG-TPGS-PLAM was investigated and compared with PAL dispersion, REG dispersion, PAL-REG dispersion and monotherapies, i.e. PAL-TPGS-PLAM and REG-TPGS-PLAM. Our results demonstrated the PS of all the tested formulations in the range of 120-190 nm, with narrow PDI of 0.2-0.3 and ZP of-18 to-30 mV. SEM analysis exhibited spherical shaped nanomicelles with uniform distribution. Polymerization of the TPGS-PLA was confirmed by the FTIR, (HNMR)-H-1 and DSC. In-vitro drug release profiles of PAL-REG-TPGS-PLAM and the mon-otherapies of PAL-TPGS-PLAM and REG-TPGS-PLAM showed significantly sustained pattern of the drug release when compared with pure drug dispersions of PAL and REG. In-vitro cell lines studies showed significantly reduced cell viability (p < 0.05) in H69PR cells, when treated with PAL-TPGS-PLAM, REG-TPGS-PLAM and PAL-REG-TPGS-PLAM as compared to blank TPGS-PLAM and respective drug dispersion. However, PAL-REG-TPGS-PLAM demonstrated more significant (p < 0.01) antitumor results then the former groups. It can be concluded that PAL-REG-TPGS-PLAM is capable of improved antitumor effect of PAL and REG, most probably due to their synergistic effects and targeted drug delivery.