Formulation and in vitro Evaluation of Targeted Chemotherapy of Crizotinib-loaded polymeric Nanoparticles on Cancer Cell Lines.

Abstract

Introduction: Crizotinib, an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, holds significant potential for the treatment of lung cancer. However, its toxicities present a major challenge to its clinical use. To enhance the targeted delivery of Crizotinib to lung tumors, polymeric-based nanoparticles were developed.

Methods: Crizotinib-loaded polymeric nanoparticles were prepared using a nano-precipitation method, incorporating stearic acid as the lipid, polyethylene glycol as the polymer, and Tween 80 as the surfactant. Key formulation parameters were optimized to achieve high-quality nanoparticles.

Results: The optimized formulation exhibited a mean particle size of 142 nm, a zeta potential of -31.9 mV, an entrapment efficiency of 82.35%, and an in vitro drug release of 60.69%. These nanoparticles were then tested on lung cancer cell lines to assess their cytotoxicity, apoptosis induction, and anti-proliferative effects on the cell cycle. In vitro studies confirmed that the Crizotinib-loaded nanoparticles exerted targeted effects on nonsmall cell lung carcinoma (NSCLC) cell lines, showing maximum inhibitory effects. One year of storage at 4°C, stability testing demonstrated that the lyophilized nanoparticles maintained their effectiveness.

Discussion: crizotinib nano-formulations were assessed for a variety of physicochemical and in vitro characterization . Five different formulations were designed and optimized on the basis of Particle size, Zeta potential, %EE, and in vitro drug release. Optimum formulation also showed maximum inhibitory effect on the cancer cell line.

Conclusion: This nanotechnology approach offers a promising targeted drug delivery system for Crizotinib, characterized by small particle size, high encapsulation efficiency (EE), and optimal in vitro drug release.