β-Glucan-Mediated Oral Codelivery of 5FU and Bcl2 siRNA Attenuates Stomach Cancer

Area of Science:

• Oncology
• Biomaterials Science
• Drug Delivery Systems

Background:

• Stomach cancer is a leading cause of cancer death, particularly among Hispanic populations.
• Current treatments for stomach cancer have poor outcomes due to lack of early diagnosis and targeted therapies.
• Existing treatments are invasive and delivered systemically, despite the localized nature of early-stage gastric cancer.

Purpose of the Study:

• To develop and evaluate an oral local delivery approach for enhanced stomach cancer therapy.
• To investigate the efficacy of a beta-glucan (BG)-based oral vehicle for prolonged gastric retention and controlled drug release.
• To assess the combined therapeutic effect of Bcl2 siRNA and 5-fluorouracil (5FU) delivered via the BG vehicle.

Main Methods:

• Development of a beta-glucan (BG)-based oral delivery vehicle capable of mucus adhesion and controlled release.
• In vitro assessment of siRNA stability in simulated gastric conditions.
• In vivo evaluation in a C57BL/6 stomach cancer mouse model using various treatment groups (5FU, BG/5FU, siRNA, BG/siRNA, BG/5FU/siRNA).
• Analysis of therapeutic efficacy using Western blotting, TUNEL assay, histology (H&E), and immunohistochemistry (Ki67, TUNEL, Bcl2).

Main Results:

• The BG vehicle successfully adhered to the stomach mucus, providing sustained release of Bcl2 siRNA and 5FU for over 6 hours.
• Bcl2 siRNA demonstrated selective gene knockdown in the stomach cancer mouse model, leading to increased apoptosis.
• The combined BG/5FU/siRNA treatment showed superior inhibition of Bcl2 and enhanced therapeutic efficacy compared to individual treatments.
• Histological and immunohistochemical analyses confirmed significant tumor reduction and apoptosis induction in the BG/5FU/siRNA group.
• The oral formulation exhibited improved efficacy with minimal side effects in the gastric cancer mouse model.

Conclusions:

• An oral beta-glucan-based delivery system offers a promising strategy for localized stomach cancer treatment.
• This approach enhances therapeutic efficacy by prolonging drug retention in the stomach and enabling targeted delivery of siRNA and chemotherapy.
• The developed oral formulation demonstrates improved outcomes and reduced side effects compared to conventional systemic treatments for gastric cancer.