<p>Nanoparticle-Mediated Drug Delivery Systems For The Treatment Of IBD: Current Perspectives</p>

Abstract

Inflammatory bowel disease (IBD), which mainly consists of Crohn's disease and ulcerative colitis, is a chronic and relapsing inflammatory condition of the gastrointestinal tract. The traditional treatment strategies relied on frequent administration of high dosages of medications, including antibiotics, non-steroidal anti-inflammatory drugs, biologics, and immunomodulators, with the goal of reducing inflammation. Some of these medications were effective in alleviating the early-stage inflammatory symptoms, but their long-term efficacies were compromised by the accumulation of toxicities. Recently, nanoparticle (NP)based drugs have been widely studied for their potential to solve such problems. Various mechanisms/strategies, including size-, charge-, pH-, pressure-, degradation-, ligand-receptor-, and microbiome-dependent drug delivery systems, have been exploited in preclinical studies. A certain number of NP delivery systems have sought to target drugs to the inflamed intestine. Although several NP-based drugs have entered clinical trials for the treatment of IBD, most have failed due to premature drug release, weak targeting ability, and the high immune toxicity of some of the synthetic nanomaterials that have been used to fabricate the NPs. Therefore, there is still a need for rationally designed and stable NP drug delivery system that can specifically target drugs to the disease site, prolong the drug's residence time, and minimize systemic side effects. This review will analyze the current state of the art in NP-mediated drug delivery for IBD treatment. We will focus on topics such as deliverable targets (at the tissue or cellular level) for treating inflammation; the target-homing NP materials that can interact with such targets; and the major administration routes for treating IBD. These discussions will integrate notable trends in the research and development of IBD medications, including multi-responsive NP-mediated delivery and naturally-derived targeting NPs. Finally, current challenges and future directions will be presented in the hopes of advancing the study of NP-mediated strategies for treating IBD.

Anti-Inflammatory Effects of Rosmarinic Acid-Loaded Nanovesicles in Acute Colitis through Modulation of NLRP3 Inflammasome

“…On the other hand, the poor water solubility and low bioavailability limited the clinical use of this polyphenol [23]. The application of nanosystems based on colon targeted drug delivery is receiving considerable attention for local treatment of UC since they can decrease drug loss in proximal intestine and thus increase drug concentration in the colon [34]. Conventional nanovesicles are scarcely used since they can suffer from gastric and enzymatic degradation, reducing the drug oral bioavailability.…”

Drug Disposition in the Lower Gastrointestinal Tract: Targeting and Monitoring

“…Extrapolation to humans remains to be explored. Nanosized drug carriers may also result in increased penetration in the mucus layer [ 104 , 105 , 106 ]. In addition to the reduced size, the type of nanomaterial and shape can also be modified depending on the clinical applications.…”

Chronic Inflammatory Diseases, Anti-Inflammatory Agents and Their Delivery Nanosystems

“…A certain number of NP delivery systems have sought to target drugs to the inflamed intestine. Although several NP-based drugs have entered clinical trials for the treatment of IBD, most have failed due to premature drug release, weak targeting ability, and the high immune toxicity of some of the synthetic nanomaterials that have been used to fabricate the NPs [ 102 , 103 , 104 , 105 , 106 ]. Additionally, numerous in vitro and in vivo experiments have demonstrated that not only nanoscaled synthetic drugs, but also phytochemicals and macromolecules encapsulated in nanoparticles can be used for the treatment of IBD and IBD-associated colorectal cancer [ 51 , 107 , 108 ].…”