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 IC₅₀ 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.

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Materials

Gefitinib was purchased from Beijing Mesochem Technology Co. Ltd. (Beijing, China). Pluronic-F68 (PF-68, HLB: 29) and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) were purchased from Sigma Aldrich, St. Louis, MO, USA. Tween-80 (T-80, HLB: 15) was purchased from Loba Chemie (Mumbai, India). Stearic acid (SA, long-chain fatty acid) and Tween-20 (T-20, HLB: 16.7) were purchased from BDH (Poole, UK). Kolliwax-GMS (K-GMS, which contains mainly mono-glyceride) was donated by BASF (Ludwigshafen, Germany). Compritol −888 (C-888, mainly di-glyceride) was purchased from Sigma Chemicals Co. (St. Louis, Missouri).

Sherif AY, Harisa GI, Alanazi FK, Nasr FA, Alqahtani AS. PEGylated SLN as a Promising Approach for Lymphatic Delivery of Gefitinib to Lung Cancer. Int J Nanomedicine. 2022;17:3287-3311
https://doi.org/10.2147/IJN.S365974