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:

• intestinal bowel disease
• nanoparticle
• multi-responsive
• edible-plant derived
• exosome
• targeted drug delivery

Acknowledgments

This work was supported by the National Institutes of Health of Diabetes and Digestive and Kidney (RO1-DK-116306 and RO1-DK-107739 to D.M.), the Department of Veterans Affairs (Merit Award BX002526 to D.M.). DM is a recipient of a Senior Research Career Scientist Award (BX004476) from the Department of Veterans Affairs. Authors appreciate the support from the Royal Society of Chemistry for reusing of Figure 3, the structure of edible-plant derived nanoparticles, from the Journal of Materials Chemistry B, 2018; 6(9): 1312-1321.

Abbreviations

IBD, inflammatory bowel disease; ICAM, intercellular adhesion molecule; NP, nanoparticle; VCAM, vascular cell adhesion molecule; DDS, drug delivery system; PSGL-1, P-selectin glycoprotein ligand-1; GI, gastrointestinal; PLA, poly lactic acid; UC, ulcerative colitis; PLGA, poly lactic-co-glycolic acid; CD, Crohn’s disease; β7 I, β7 integrin; TNF, tumor necrosis factor; CyD1, Cyclin D 1; IV, intravenous; PE, phosphatidylethanolamine; SC, subcutaneous; PC, phosphatidylcholine; siRNA, small interfering RNA; Tregs, regulatory T cells; EPR, enhanced permeability effect; Ths, helper T cells; IECs, intestinal epithelial cells; IL-10, interleukin-10; TJs, tight junctions; GDLP, ginger derived lipid nanoparticle; QDs, quantum dots; LGG, lactobacillus rhamnosus; PepT1, peptide transporter 1; I3A, indole-3-carboxaldehyde; PEG, poly ethylene glycol; GDNPs, ginger derived nanoparticles; DCs, dendritic cells; GPCR, G-protein coupled receptor; ECM, extracellular matrix; IM, intramuscular; IFNs, interferons; ASO, antisense oligonucleotide; TGF-β, transforming growth factor- β; LMWC, low molecular weight chitosan; MMP, matrix metalloproteinases; TNBS, 2,4,6-trinitrobenzene sulfonic acid; MPO, myeloperoxidase; PK, pharmacokinetics; ROS, reactive oxygen species; SCFAs, short-chain fatty acids; RNS, reactive nitrogen species; MGL, macrophage galactose/N-acetylgalactosamine-specific lectins; GM-CSF, granulocyte-macrophage colony-stimulating factor; G-MDSC, granulocytic myeloid-derived suppressor cells; STAT3, signal transducer and activator of transcription 3.

Author Contributions

All authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.