Oral Delivery of RNAi for Cancer Therapy

Authors

Humayra Afrin
Renu Geetha Bai
Raj Kumar
Sheikh Shafin Ahmad
Sandeep K Agarwal
Md Nurunnabi

Publication Date

9-1-2023

Journal

Cancer and Metastasis Reviews

DOI

10.1007/s10555-023-10099-x

PMID

36971908

PMCID

PMC10040933

PubMedCentral® Posted Date

3-27-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, RNA Interference, RNA, Small Interfering, Neoplasms, Carcinogenesis, Drug Delivery Systems, Oral RNAi, RNAi therapeutics, Oral medicines, Cancer, Bioengineering

Abstract

Cancer is a major health concern worldwide and is still in a continuous surge of seeking for effective treatments. Since the discovery of RNAi and their mechanism of action, it has shown promises in targeted therapy for various diseases including cancer. The ability of RNAi to selectively silence the carcinogenic gene makes them ideal as cancer therapeutics. Oral delivery is the ideal route of administration of drug administration because of its patients' compliance and convenience. However, orally administered RNAi, for instance, siRNA, must cross various extracellular and intracellular biological barriers before it reaches the site of action. It is very challenging and important to keep the siRNA stable until they reach to the targeted site. Harsh pH, thick mucus layer, and nuclease enzyme prevent siRNA to diffuse through the intestinal wall and thereby induce a therapeutic effect. After entering the cell, siRNA is subjected to lysosomal degradation. Over the years, various approaches have been taken into consideration to overcome these challenges for oral RNAi delivery. Therefore, understanding the challenges and recent development is crucial to offer a novel and advanced approach for oral RNAi delivery. Herein, we have summarized the delivery strategies for oral delivery RNAi and recent advancement towards the preclinical stages.