Oral Nanomedicines for siRNA Delivery to Treat Inflammatory Bowel Disease

Abstract

RNA interference (RNAi) therapies have significant potential for the treatment of inflammatory bowel diseases (IBD). Although administering small interfering RNA (siRNA) via an oral route is desirable, various hurdles including physicochemical, mucus, and cellular uptake barriers of the gastrointestinal tract (GIT) impede both the delivery of siRNA to the target site and the action of siRNA drugs at the target site. In this review, we first discuss various physicochemical and biological barriers in the GI tract. Furthermore, we present recent strategies and the progress of oral siRNA delivery strategies to treat IBD. Finally, we consider the challenges faced in the use of these strategies and future directions of oral siRNA delivery strategies.

Attenuation of Chronic Inflammation in Intestinal Organoids with Graphene Oxide-Mediated Tumor Necrosis Factor-α_Small Interfering RNA Delivery

“…This model serves as a valuable tool for investigating the mechanisms underlying chronic inflammation and evaluating potential therapeutic interventions. 7,41,71 smGO-Mediated siRNA Delivery. After successfully inducing a proinflammatory phenotype in the intestinal organoids, we proceeded to evaluate the gene silencing of TNF-α with a GO-mediated TNF-α_siRNA transfection approach.…”

“…In summary, these findings collectively establish the successful induction of a robust inflammatory phenotype closely resembling that observed in IBD. This model serves as a valuable tool for investigating the mechanisms underlying chronic inflammation and evaluating potential therapeutic interventions. ,, …”

“…10 Anti-TNF-α antibodies, such as infliximab, adalimumab, and golimumab, have been successfully implemented in the treatment of IBD. 7,11 However, antibody therapeutic modalities have limitations, including the risk of infections, demyelinating diseases, and induction of autoimmune diseases due to systemic cytokine depletion. 7,12 A viable alternative to systemic antibody administration is the gene silencing of target inflammatory cytokines via transient small interfering RNAs (siRNAs).…”

“…7,11 However, antibody therapeutic modalities have limitations, including the risk of infections, demyelinating diseases, and induction of autoimmune diseases due to systemic cytokine depletion. 7,12 A viable alternative to systemic antibody administration is the gene silencing of target inflammatory cytokines via transient small interfering RNAs (siRNAs). Gene silencing of TNF-α has shown downregulation of MMPs and a reduction in paw swelling and joint destruction in rheumatoid arthritis mouse models.…”

Syringic Acid Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulating Gut Microbiota

“…The gut microbiota is known to have a critical role in regulating immune responses, aiding in digestion, facilitating nerve signaling, and promoting angiogenesis, while also defending against pathogens. 43 When the gut microbiota is imbalanced or dysbiotic, it can result in various ailments, such as cancer, 44 cardiovascular disease, 45 and IBD. 46 With this in mind, we undertook 16S rRNA sequencing to further explore the restorative effects of SA on the gut microbiota of mice with DSS-induced colitis.…”