Nanoparticle-Mediated Drug Delivery Systems For The Treatment Of IBD: Current Perspectives

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.

Keywords: edible-plant derived; exosome; intestinal bowel disease; multi-responsive; nanoparticle; targeted drug delivery.

Figure 1

Mucus layer, epithelium, and lamina propria of the small and large intestine.

Figure 2

Orally delivery or injection of NPs to the inflamed intestinal epithelium with impaired epithelial cells and permeable blood vessel.

Figure 3

Structures of plant-derived nanoparticles (PDNPs), exosome, and synthetic nanoparticles (artificial liposomes). (A) Major forms of PDNPs, (B) mammalian exosome, and (C) major forms of the artificial liposomes. Reprinted with permission from The Royal Society of Chemistry. Yang C, Zhang M, Merlin D. Advances in plant-derived edible nanoparticle-based lipid nano-drug delivery systems as therapeutic nanomedicines. J Mater Chem B. 2018;6(9):1312–1321.