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

Abstract

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.

Optimization of Gefitinib-Loaded Nanostructured Lipid Carrier as a Biomedical Tool in the Treatment of Metastatic Lung Cancer

“…The presence of GEF in solid lipids instead of liquid oil resulted in the disruption of SA crystallization. In a similar context, Sherif et al found that the incorporation of a drug within a solid lipid resulted in a disruption in SA crystallinity [ 2 ]. Regarding ZP, the incorporation of GEF resulted in increased ZP value in the case of GEF-NLC (LCT) .…”

“…Moreover, in our previous work, GEF-SLN formulation contained a solid lipid only where GEF was expected to be homogenously distributed within SA ( Figure 9 ). An in vitro release study revealed that about 74% of the drug was released within 24 h [ 2 ]. Herein, about 50% GEF was released within 24 h from GEF-NLC (LCFA) .…”

“…The significant increase in the PS of GEF-NLC (LCT) could be attributed to the predominant presence of GEF in solid lipids instead of liquid oil. This resulted in drug expulsion from solid lipids owing to reported SA recrystallization during storage [ 2 ]. This is in accordance with a previously reported study where the deformation of nanoparticles resulted in particle aggregation [ 30 ].…”

“…Tyrosine kinases play an important role in cell proliferation by affecting signaling pathways, DNA repair, and programmed cell death [ 1 ]. Therefore, tyrosine kinase inhibitors are used during the treatment of different types of cancer [ 2 ]. Among them, gefitinib (GEF, abbreviations listed in Table S1 ) is approved for the treatment of non-small cell lung cancer [ 3 ].…”

“…Among them, gefitinib (GEF, abbreviations listed in Table S1 ) is approved for the treatment of non-small cell lung cancer [ 3 ]. It belongs to class II according to biopharmaceutical classification systems, with a Log p value of (3.2); it is highly hydrophobic with low solubility [ 2 ]. GEF has an oral bioavailability of around 44%, which delays its onset of action and requires increasing the dose [ 4 ].…”