Receptor-mediated targeted drug delivery systems for treatment of inflammatory bowel disease: Opportunities and emerging strategies

Abstract

Inflammatory bowel disease (IBD) is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization. With no curative therapy for IBD at present, the development of effective therapeutics is highly advocated. Drug delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention (EPR) effect caused by the inflammation. However, the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug release. Substantial researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs, ligand-modified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative effects. This review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ligands. Finally, challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD.

Keywords: ACQ, aggregation-caused quenching; ADR, adverse drug reaction; AIE, aggregation-induced emission; Active target; BSA, bovine serum albumin; CAM, cell adhesion molecule; CD, Crohn's disease; CRD, cysteine-rich domain; CS, chondroitin sulfate; CT, computed tomography; CTLD, c-type lectin-like domain; Cell adhesion molecule; Crohn's disease; DCs, dendritic cells; DSS, dextran sulfate sodium salt; Drug delivery; EGF, epidermal growth factor; EPR, enhanced permeability and retention; FNII, fibronectin type II domain; FR, folate receptor; FRET, fluorescence resonance energy transfer; GIT, gastrointestinal tract; HA, hyaluronic acid; HUVEC, human umbilical vein endothelial cells; IBD, inflammatory bowel disease; ICAM, intercellular adhesion molecule; Inflammatory bowel disease; LMWC, low molecular weight chitosan; LPS, lipopolysaccharide; MAP4K4, mitogen-activated protein kinase kinase kinase kinase 4; MGL, macrophage galactose lectin; MPO, myeloperoxidase; MPS, mononuclear phagocyte system; MR, mannose receptor; MRI, magnetic resonance imaging; PAMAM, poly(amidoamine); PEI, polyethylenimine; PSGL-1, P-selectin glycoprotein ligand-1; PepT1, peptide transporter 1; QDs, quantum dots; RES, reticuloendothelial system; Receptor-mediated target; Targeted therapy; TfR, transferrin receptor; UC, ulcerative colitis; Ulcerative colitis; VCAM, vascular cell adhesion molecule.