Formulation Design, Optimization, and In Vitro Evaluation of Palbociclib-Loaded Polymeric Nanoparticles

Palbociclib (PLB), an advanced breast cancer drug, shows limited success in clinical scenarios due to toxicity and resistant antitumor activities. The article aimed at preparing folic acid-modified chitosan-based polymeric nanoparticles (PNS) for controlled and targeted release of PLB. PLB-loaded nanoparticles were prepared via solvent evaporation. Central composite design was adopted in optimizing the formulation, with concentration levels of chitosan and polyvinyl alcohol (PVA) making responses of size and zeta potential (ZP) its independent variables. Mean particle size (MPS) ranged from 376 to 412 nm, and ZP ranged from 29.87 to 36.76 mV. Quadratic models were significant for both responses (MPS: F = 9.81, p = 0.0128; ZP: F = 5.24, p = 0.0466), with a nonsignificant lack of fit, confirming model adequacy. Particle size was significantly influenced by chitosan and PVA quadratic terms, while ZP was primarily affected by PVA. Optimization predicted a formulation with 63.35 mg of chitosan, 20 mg of PVA, an MPS of 389.1 nm, and a ZP of 31.2 mV, closely matching experimental observations (MPS of 237.8 ± 1.76 nm and ZP of 32.09 ± 3.38 mV). Entrapment efficiency and drug loading were 81.21 ± 1.80% and 40.79 ± 1.98%, respectively. PLB-PNS exhibited sustained, pH-responsive release, releasing 70.48% at pH 5.4 and 50.77% at pH 7.4 at 12 h, while free drug released 97.20% and 91.52%, respectively, confirming controlled and tumor-microenvironment-responsive drug delivery. Drug release followed Korsmeyer-Peppas kinetics, indicating diffusion-controlled release. Scanning electron microscope analysis revealed smooth, spherical nanoparticles. These developed PLB-loaded nanoparticles were indicated as an attractive tumor microenvironment-responsive drug-delivery carrier system capable of achieving enhanced therapeutic outcomes in breast cancer therapy.