Anti-Tumor Activity of Orally Administered Gefitinib-Loaded Nanosized Cubosomes against Colon Cancer

Abstract

Gefitinib (GFT) is a tyrosine kinase inhibitor drug used as a first-line treatment for patients with advanced or metastatic non-small cell lung, colon, and breast cancer. GFT exhibits low solubility and hence low oral bioavailability, which restricts its clinical application. One of the most important trends in overcoming such problems is the use of a vesicular system. Cubosomes are considered one of the most important vesicular systems used to improve solubility and oral bioavailability. In this study, GFT cubosomal nanoparticles (GFT-CNPs) were prepared by the emulsification method. The selected formulation variables were analyzed and optimized by full factorial design and response surface methodology. Drug entrapment efficiency (EE%), transmission electron microscopy, particle size, polydispersity index, in vitro release and its kinetics, and the effect of storage studies were estimated. The chosen GFT-CNPs were subjected to further investigations as gene expression levels of tissue inhibitors of metalloproteinases-1 (TIMP-1) and matrix metalloproteinases-7 (MMP-7), colon biomarkers, and histopathological examination of colon tissues. The prepared GFT-CNPs were semi-cubic in shape, with high EE%, smaller vesicle size, and higher zeta potential values. The in vivo data showed a significant decrease in the serum level of embryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), and gene expression level of TIMP-1 and MMP-7. Histopathological examination showed enhancement in cancer tissue and highly decreased focal infiltration in the lamina propria after treatment with GFT-CNPs.

Lipid-based oral formulation in capsules to improve the delivery of poorly water-soluble drugs

“…Histopathological analysis after GFT-CNPs treatment showed a rise in cancer tissue and noticeably less localised infiltration in the lamina propria. According to this study's findings, GFTCNPs could be used as an oral vesicular system to treat colon cancer (El-Shenawy et al, 2023).…”

Development and optimization of vildagliptin solid lipid nanoparticles loaded ocuserts for controlled ocular delivery: A promising approach towards treating diabetic retinopathy

“…That objective was achieved by the dual coating of the drug reservoir by Eudragit RL100 in a rat-controlling membrane (RCM). This RCM slows eroding, reducing VLD release in addition to HPMC in the inner core, which controls the VLD release rate ( El-Rasoul and Ahmed, 2010 ; El-Shenawy et al, 2023 ). Eq.…”

“…The droplet was visualized under SEM (SMM-5400 LV–SEM) (Jeol, Japan) and photographed. The SEM was operating at 15.0 KV ( Abdelhameed et al, 2022 ; El-Shenawy et al, 2023 ).…”

“…Samples were precisely weighed into aluminum pans and sealed. All samples were run at a heating rate of 10 °C/min over a temperature range of 25–300 °C under an atmosphere of nitrogen, and the DSC thermograms were recorded ( El-Shenawy et al, 2023 ; Hasan et al, 2020 ).…”

The loss of B7-H4 expression in breast cancer cells escaping from T cell cytotoxicity contributes to epithelial-to-mesenchymal transition

“…Chemoresistance is a typical phenotype in the acquisition of malignancy in breast tumor and is directly associated with the stemness of breast cancer cells. For further mechanistic insights into the role of B7-H4 in breast cancer cell chemoresistance, the chemosensitivity of Doxorubicin [ 30 ], Oxaliplatin [ 31 , 32 ], Fluorouracil [ 33 ] and Gefitinib [ 34 ] was investigated in B7-H4-KO and B7-H4-OE cells by evaluating the IC50 values. These compounds are widely used therapies in treating breast cancer patients.…”