Nanoparticle-based therapeutics of inflammatory bowel diseases: a narrative review of the current state and prospects

Abstract

Inflammatory bowel disease (IBD), such as Crohn disease and ulcerative colitis, are chronic relapsing disorders of the gastrointestinal tract. Characterized pathologically by intestinal inflammation and epithelial injury, great challenges exist for the treatment of IBD due to its complicated etiology and incurable nature. Traditional strategies rely on frequent and long-term administration of high dosages of anti-inflammatory drugs, which inevitably cause side effects. Therefore, novel therapeutic methods and drug delivery systems capable of improving therapeutic effect while simultaneously decreasing side effects need to be developed. The emergence of nanotechnology provides alternative approaches for diagnosis and treatment of IBD, as nanoparticles (NPs) have unique physicochemical properties such as targeting to the site of inflammation and the ability to alter the pharmacokinetics of traditional drugs. This review first introduces the pathophysiological features and microenvironment of IBD, and then summarizes different strategies and mechanisms of NP-based colon-targeted drug delivery systems, including size-dependent, multi-stimuli responsive, active targeting, intestinal microbiota-related, and novel natural-derived NP-mediated drug delivery systems. We also discuss applications of nanozymes and NP-based imaging in diagnostics and treatment of IBD. Finally, challenges and prospects in the field are proposed to promote the development of targeted drug delivery for IBD treatment.

Oral Delivery of Pterostilbene by L-Arginine-Mediated “Nano-Bomb” Carrier for the Treatment of Ulcerative Colitis

“…HA can selectively bind to CD44 and block its release of a drug because of its large and biocompatible molecular size, not to mention its ability to be readily degraded by HAase after being taken up by cells. 48 Interestingly, HA NPs loaded with L-Arg could also reduce the expression of pro-inflammatory cytokines both in vitro and in vivo to a certain extent, which was consistent with previous report. 49,50 Shreds of evidence show that L-Arginine regulates the progression of IBD through the oxidative system, intestinal immunity, intestinal microbiota, tight junction proteins, and metabolic products, like nitric oxide (NO) and polyamines.…”

Advances in the treatment of inflammatory bowel disease: Focus on polysaccharide nanoparticulate drug delivery systems

“…They combine the advantages of nanoparticulate systems with intrinsic biological activities of polysaccharides. On one side, the nanoparticles offer different functionalities such as mucoadhesion, mucopenetration, passive targeting of inflamed tissues in the GI tract, and capture by the immune cells (For review articles on nanoparticles used for IBD, see references [16][17][18][19][20][21][22] ). On the other hand, polysaccharides exhibit intrinsic biological activity such as anti-inflammatory, healing, immunomodulation, and regulation of the intestinal microbiota (For a review article on polysaccharide-based DDS for IBD, see reference 23 .…”

Oral Delivery of Biologics in Inflammatory Bowel Disease Treatment

“…In another study, the accumulation of 40 nm core-shell-type micelles (RPN°) formed by a new redox polymer in the inflamed area were evaluated in a DSS-induced colitis model in ICR mice, showing a greater accumulation in the inflamed area without absorption to the bloodstream ( Vong et al, 2012 ). Different inflammatory markers can also be used as a target such as CD98, CD44, and folate and mannose receptor, all overexpressed on the surface of colon epithelial cells and macrophages and peptide transporter-1 (Pept1) to target macrophages ( Yang et al, 2020 ). Recently, hyaluronic acid has been used to selectively target CD44 ( Misra et al, 2015 ; Lee Y. et al, 2020 ) while lysine-proline-valine (KPV), a C-terminal peptide fragment of a α-melanocyte-stimulating hormone, can target Pept1 ( Wu et al, 2019 ).…”

“…Recently, NPs synthesized with natural products have been developed to overcome problematic issues of polymeric NPs such as toxicity and scale up for their synthesis ( Yang et al, 2020 ). Some of the examples are ginger-derived nanolipids developed for short-interfering RNA (siRNA) delivery against CD98 ( Zhang et al, 2017 ) and Lycium barbarum -lipid-based NPs which present excellent anti-inflammatory properties ( Zu et al, 2020 ).…”

“…Healthy individuals present a significant different microbiota compared with individuals with IBD, who present a decrease in commensal bacteria diversity, abnormal composition, and altered spatial distribution ( Khan et al, 2019 ; Guo et al, 2020 ). Studies showed that some metal NPs that could regulate the intestinal microbiota reduced IBD symptoms ( Yang et al, 2020 ). Nowadays, synbiotics, a combination of pre- and probiotics are being tested for IBD treatment; however, only few studies are available ( Khan et al, 2019 ).…”