Colon-Targeted Sustained-Release Combinatorial 5-Fluorouracil and Quercetin poly(lactic- co-glycolic) Acid (PLGA) Nanoparticles Show Enhanced Apoptosis and Minimal Tumor Drug Resistance for Their Potential Use in Colon Cancer

Ahmed Kh Abosalha; Paromita Islam; Jacqueline L Boyajian; Rahul Thareja; Sabrina Schaly; Amal Kassab; Stephanie Makhlouf; Sarah Alali; Satya Prakash

doi:10.1021/acsptsci.4c00462

Colon-Targeted Sustained-Release Combinatorial 5-Fluorouracil and Quercetin poly(lactic- co-glycolic) Acid (PLGA) Nanoparticles Show Enhanced Apoptosis and Minimal Tumor Drug Resistance for Their Potential Use in Colon Cancer

ACS Pharmacol Transl Sci. 2024 Aug 20;7(9):2612-2620. doi: 10.1021/acsptsci.4c00462. eCollection 2024 Sep 13.

Authors

Ahmed Kh Abosalha^{1

2}, Paromita Islam¹, Jacqueline L Boyajian¹, Rahul Thareja¹, Sabrina Schaly¹, Amal Kassab¹, Stephanie Makhlouf¹, Sarah Alali¹, Satya Prakash¹

Affiliations

¹ Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine and Health Sciences, McGill University, Montreal, Quebec H3A 2B4, Canada.
² Pharmaceutical Technology Department, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt.

PMID: 39296268
PMCID: PMC11406683 (available on 2025-08-20)
DOI: 10.1021/acsptsci.4c00462

Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide, acting as a significant public health problem. 5-Fluorouracil (5-FU) is a key chemotherapy for various types of cancer, due to its broad anticancer activity. However, the emergence of drug resistance is a considerable limitation in the clinical application of 5-FU. Quercetin (QC) is proposed as an adjuvant therapy to minimize drug resistance to chemotherapeutics and enhance their pharmacological efficacy. The oral delivery of 5-FU and QC is challenged by poor aqueous solubility of QC and poor cellular permeability of 5-FU. To solve this issue, novel polylactide-co-glycolide (PLGA) combinatorial nanoparticles loading 5-FU and QC were prepared to deliver them directly to the colon. These sustained-release combinatorial nanoparticles recorded a significant decrease in cancer cell proliferation, C-reactive protein (CRP) level, and Interleukin-8 (IL-8) expression by 30.08%, 40.7%, and 46.6%, respectively. The results revealed that this combination therapy may offer a new strategy for the targeted delivery of chemotherapeutics to the colon.