Optimization and In-vitro Evaluation of Cisplatin-Loaded Chitosan Nanoparticles against Lung Cancer Cell Lines
Keywords:
Cisplatin encapsulation, Chitosan nanocarriers, Pulmonary carcinoma, Targeted delivery, A549 cells, H460 cellsAbstract
Pulmonary malignancy continues to represent a major global health burden with significant therapeutic challenges. Traditional cisplatin chemotherapy is hampered by severe adverse effects and suboptimal tumor targeting. This investigation focused on engineering cisplatin-encapsulated chitosan nanocarriers (Cis-Chi-NCs) to improve therapeutic outcomes while minimizing systemic toxicity. The nanocarriers were synthesized through tripolyphosphate-mediated ionic crosslinking methodology. Formulation parameters were systematically optimized employing response surface methodology to examine the influence of polymer concentration, crosslinker content, and drug-loading ratio on nanocarrier properties. The optimized formulation achieved particle dimensions of 185.4 ± 12.3 nm, polydispersity of 0.24 ± 0.03, surface charge of +28.6 ± 2.1 mV, and encapsulation efficiency of 78.2 ± 4.5%. Biological assessment using A549 and H460 pulmonary carcinoma models revealed markedly superior antineoplastic activity versus free cisplatin, demonstrating IC50 concentrations of 2.8 ± 0.3 μM and 3.2 ± 0.4 μM respectively. Fluorescence-based cellular internalization studies confirmed enhanced uptake mechanisms. Flow cytometric apoptosis evaluation demonstrated elevated programmed cell death compared to conventional therapy. These findings indicate that chitosan-based nanocarrier systems offer promising potential for targeted pulmonary cancer intervention with improved efficacy and reduced toxicity profiles
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