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

Int J Nanomedicine. 2022 Jul 28:17:3287-3311. doi: 10.2147/IJN.S365974. eCollection 2022.

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 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.

Keywords: PEGylated SLN; apoptosis; cytotoxicity; gefitinib; intestinal permeability; solid lipid nanoparticles.

MeSH terms

  • Animals
  • Drug Carriers / chemistry
  • Gefitinib / therapeutic use
  • Lipids / chemistry
  • Liposomes
  • Lung Neoplasms* / drug therapy
  • Lymphatic System
  • Nanoparticles* / chemistry
  • Particle Size
  • Polyethylene Glycols / therapeutic use
  • Rabbits

Substances

  • Drug Carriers
  • Lipid Nanoparticles
  • Lipids
  • Liposomes
  • Polyethylene Glycols
  • Gefitinib

Grants and funding

The authors extend their appreciation to the Deanship of Scientific Research, King Saud University for funding through Vice Deanship of Scientific Research Chairs, Kayyali Chair for Pharmaceutical Industry, Department of Pharmaceutics, College of Pharmacy, for funding the work through Grant Number AG-2022.