PEGylated SLN as a Promising Approach for Lymphatic Delivery of Gefitinib to Lung Cancer

PURPOSE: The present study aimed to develop gefitinib-loaded solid lipid nanoparticles (GEF-SLN), and GEF-loaded PEGylated SLN (GEF-P-SLN) for targeting metastatic lung cancer through the lymphatic system. METHODS: The prepared SLNs were characterized in terms of physicochemical properties, entrapment efficiency, and in-vitro release. Furthermore, ex-vivo permeability was investigated using the rabbit intestine. Cytotoxicity and apoptotic effects were studied against A549 cell lines as a model for lung cancer. RESULTS: The present results revealed that the particle size and polydispersity index of the prepared formulations range from 114 to 310 nm and 0.066 to 0.350, respectively, with negative zeta-potential (−14 to −27.6). Additionally, SLN and P-SLN showed remarkable entrapment efficiency above 89% and exhibited sustained-release profiles. The permeability study showed that GEF-SLN and GEF-P-SLN enhanced the permeability of GEF by 1.71 and 2.64-fold, respectively, compared with GEF suspension. Cytotoxicity showed that IC(50) of pure GEF was 3.5 μg/mL, which decreased to 1.95 and 1.8 μg/mL for GEF-SLN and GEF-P-SLN, respectively. Finally, the apoptotic study revealed that GEF-P-SLN decreased the number of living cells from 49.47 to 3.43 when compared with pure GEF. CONCLUSION: These results concluded that GEF-P-SLN is a promising approach to improving the therapeutic outcomes of GEF in the treatment of metastatic lung cancer.