Biofunctionalized polymeric nanoparticles for the enhanced delivery of erlotinib in cancer therapy.

Abstract

Erlotinib, a potent epidermal growth factor receptor (EGFR) inhibitor, faces bioavailability challenges due to poor water solubility and stability. This study aims to optimize erlotinib-loaded PLGA nanoparticles using a 3² factorial design to enhance drug delivery and therapeutic efficacy. The effects of PLGA concentration (R1) and NaTPP concentration (R2) on nanoparticle characteristics, including particle size, zeta potential, and polydispersity index (PDI), were investigated. The optimal formulation (F5) was identified and characterized, showing a particle size of 169.1 nm, a zeta potential of 20.0 mV, and a PDI of 0.146, indicating uniform and stable nanoparticles. Transmission electron microscopy (TEM) confirmed spherical nanoparticles with minimal aggregation, while X-ray diffraction (XRD) indicated an amorphous state of erlotinib. Formulation F5 demonstrated an entrapment efficiency of 81.9% and a yield of 83.0%. In-vitro drug release studies revealed a sustained release pattern with 90.0% cumulative release at 48 h, following Zero Order kinetics. Cytotoxicity assays showed low cytotoxicity across various cell lines. Statistical analysis confirmed the significant impact of formulation variables on nanoparticle properties. The systematic optimization of erlotinib-loaded nanoparticles has successfully identified formulation F5 as an optimal candidate with favorable characteristics, including minimal particle size, high stability, controlled drug release, and a safe cytotoxicity profile. Notably, the optimized formulation (F5) enhances therapeutic efficacy through improved bioavailability and targeted delivery, addressing the limitations of conventional therapies. These findings suggest that the optimized erlotinib-loaded nanoparticles hold significant potential for enhanced drug delivery and therapeutic efficacy.