Rational Design of Polyphenol-Poloxamer Nanovesicles for Targeting Inflammatory Bowel Disease Therapy

Abstract

Currently, there is no curative treatment for inflammatory bowel disease (IBD), which has an increased risk of colitis-associated cancer. Corticosteroids are the main clinical IBD therapeutics but have significant side effects. Even heavy corticosteroid use can result in the failure of IBD treatment which may lead to resective surgery. In this study, we designed one type of new drug-delivery system (DDS) delivering dexamethasone (DEX), an anti-inflammation corticosteroid, for IBD therapy. This DDS was screened by hydrogen-bonding-induced facile self-assembly of natural and safe polyphenols and polymers. The nanoparticles fabricated from tannic acid and Pluronic F-68 have a uniform spherical shape. With approximately 10% DEX loaded, PPNP-DEX showed responsive release behavior in the presence of esterase. Moreover, PPNP-DEX exhibited great potential in radical scavenging at inflammation sites. Drug retention rates can also be enhanced in mice with colitis compared with healthy controls because of this inflammation targeting ability. Owing to all these advantages, PPNP-DEX achieved remarkable treatment efficacy in colitis mice compared with PPNP or free DEX. This study demonstrates PPNP as a promising drug-delivery platform for IBD therapy. More importantly, it provides a new design strategy of therapeutics for various inflammatory diseases.

An Orally Administered CeO2@Montmorillonite Nanozyme Targets Inflammation for Inflammatory Bowel Disease Therapy

“…Stability Investigation of CeO 2 @MMT (1:9) in Simulated Gastric Juice: The stability of CeO 2 @MMT(1:9) was evaluated as follows. First, to simulate the digestion process of food in the stomach, 200 mg of CeO 2 , MMT, or CeO 2 @MMT(1:9) were added into 10 mL of hydrochloric acid solution (as a gastric fluid simulating fluid, pH at 1.2 to 1.5) and incubated at 37 °C with 65 rpm shaking for 4 h. [25] Then, CeO 2 , MMT, or CeO 2 @MMT(1:9) were neutralized by washing with water and NaOH solution (0.1 mm). Finally, the materials were dissolved in water or lyophilized for TEM, XRD, ICP, zeta potential measurements, and analysis of ROS scavenging activities.…”

Significance of Ligand-Anchored Polymers for Drug Targeting in the Treatment of Colonic Disorders

“…Owing to the unavailability of appropriate therapeutics for treatment of IBD, corticosteroids till date poses as the main clinical IBD therapeutics in spite of having significant side effects. Heavy corticosteroid use may even result in the failure of IBD treatment leading to respective surgery (Wang et al, 2018). Such drugs are administered orally.…”

“…At neutral pH both S1 and S2 remained capped, however on exposure to a reducing environment such as in the presence of sodium dithionite, payload release enhanced significantly. IBD therapy proposed by Wang et al (2018) involved a newly designed drug-delivery system that delivered an anti-inflammatory corticosteroid called dexamethasone (Dex). Study results revealed that in presence of esterase, 10% Dex loaded, PPNP-Dex (polymers self-assembled nanoparticledexamethasone) exhibited responsive release behavior.…”

Oral delivery of anti-TNF antibody shielded by natural polyphenol-mediated supramolecular assembly for inflammatory bowel disease therapy

“…The increased permeability of epithelium allows the nanoparticles to accumulate in the inflamed intestine through oral delivery 28 , 29 . In previous work, we developed polyphenol-poloxamer self-assembled supramolecular nanoparticles for oral delivery in IBD therapy 30 . Natural polyphenols such as tannic acid (TA) and epigallocatechin gallate (EGCG) are rich in galloyl and catechol groups that form hydrogen bonds and hydrophobic interactions with various proteins and peptides 31 , 32 .…”