Exemestane encapsulated polymer-lipid hybrid nanoparticles for improved efficacy against breast cancer: optimization, in vitro characterization and cell culture studies

Polymer-lipid hybrid nanoparticles (PLHNPs) are novel nanoplatforms for the effective delivery of a lipophilic drug in the management of a variety of solid tumors. The present work was designed to develop exemestane (EXE) encapsulated D-alpha-tocopheryl polyethylene glycol succinate (TPGS) based PLHNPs (EXE-TPGS-PLHNPs) for controlled delivery of EXE for breast cancer management. EXE-TPGS-PLHNPs were formulated by single-step nano-precipitation technique and statistically optimized by a 3(3) Box-Behnken design using Design expert software. The polycaprolactone (PCL; X (1)), phospholipon 90 G (PL-90G; X (2)), and surfactant (X (3)) were selected as independent factors while particles size (PS; Y (1)), polydispersity index (PDI; Y (2)), and %entrapment efficiency (%EE; Y (3)) were chosen as dependent factors. The average PS, PDI, and %EE of the optimized EXE-TPGS-PLHNPs was observed to be 136.37 +/- 3.27 nm, 0.110 +/- 0.013, and 88.56 +/- 2.15% respectively. The physical state of entrapped EXE was further validated by Fourier-transform infrared spectroscopy, differential scanning calorimetry, and powder x-ray diffraction that revealed complete encapsulation of EXE in the hybrid matrix of PLHNPs with no sign of significant interaction between drug and excipients. In vitro release study in simulated gastrointestinal fluids revealed initial fast release for 2 h after that controlled release profile up to 24 h of study. Moreover, optimized EXE-TPGS-PLHNPs exhibited excellent stability in gastrointestinal fluids as well as colloidal stability in different storage concentrations. Furthermore, EXE-TPGS-PLHNPs exhibited distinctively higher cellular uptake and time and dose-dependent cytotoxicity against MCF-7 breast tumor cells compared to EXE-PLHNPs without TPGS and free EXE. The obtained results suggested that EXE-TPGS-PLHNPs can be a promising platform for the controlled delivery of EXE for the effective treatment of breast cancer.