Design and Evaluation of Albumin‐Based Surface Functionalized Nanoparticles for Targeting Breast Cancer

Abstract Breast cancer (BC) is the second most predominant malignancy affecting women worldwide, and a variety of treatment options are available to combat this disease. The present study focused on optimizing and evaluating surface‐modified nanoparticles to enhance the therapeutic delivery of palbociclib (PCB) in targeted breast cancer cells. The palbociclib‐loaded nanoparticles were developed via the desolvation method with bovine serum albumin (BSA). The optimized formulation was obtained by applying the Box–Behnken response surface methodology. The surface was modified with folic acid and hyaluronic acid to improve the targeting specificity and cellular uptake in the MCF‐7 breast cancer cell line. The optimized formulations of folic acid‐ and hyaluronic acid‐coated nanoparticles had particle sizes of 107.76 ± 2.05, 171.20 ± 1.53, and 165.72 ± 1.45 nm; zeta potentials of −22.30 ± 1.47, −25.62 ± 1.31, and −28.52 ± 2.32 mV; and entrapment efficiencies of 85.42 ± 1.05%, 85.63 ± 2.81%, and 84.78 ± 2.67%, respectively. Drug release kinetics revealed a diffusion‐controlled mechanism characterized by Fickian diffusion ( n value = 0.4043). The in vitro cell line studies revealed that the nanoparticles coated with folic acid exhibited superior anticancer activity, achieving the lowest IC 50 value, likely due to folate receptor‐mediated targeting. These findings emphasize the potential of folic acid‐coated palbociclib nanoparticles as promising candidates for targeted breast cancer therapy.