An Orally Administered Redox Nanoparticle That Accumulates in the Colonic Mucosa and Reduces Colitis in Mice

Abstract

We designed an orally administered RNP(O) that accumulates specifically in the colons of mice with colitis and is more effective in reducing inflammation than low-molecular-weight TEMPOL or mesalamine. RNP(O) might be developed for treatment of patients with ulcerative colitis.

Development of an oral nanotherapeutics using redox nanoparticles for treatment of colitis-associated colon cancer

“…Furthermore, these 40 nm particles prevent the uptake into bloodstream via mesentery. Along with these characteristics, we have confirmed that RNP O effectively scavenges ROS to result in significant suppression of inflammation in mice with colitis [21]. Suppression of inflammation in the tumor microenvironments is reported to work as suppressor of tumor progression and resistance against chemotherapy [23].…”

“…RNP O was prepared by a self-assembling MeO-PEG-b-PMOT block copolymer, as previously reported [21,25]. Briefly, methoxy-poly(ethylene glycol)-b-poly(-chloromethylstyrene) (MeO-PEG-b-PCMS) was synthesized by the radical telomerization of chloromethylstyrene (CMS; Seimi Chemical Co., Ltd., Kanagawa, Japan) using methoxy-poly(ethylene glycol)-sulphanyl (MeO-PEG-SH; NOF Corporation Co., Ltd., Tokyo, Japan; Mn ¼ 5000) as a telogen (the degree of polymerization of CMS ¼ 16 units).…”

“…On the other hand, it has been reported that nanocomposites such as silver nanoparticle for therapeutics itself exhibits the undesired toxicity on the GI tract after repeated oral administration [19,20]. Recently, we have developed an oral nanotherapy using a redox nanoparticle (RNP O ) for suppressing inflammation in mice with colitis [21] and indomethacin-induced small intestinal inflammation [22]. RNP O was prepared by selfassembly of methoxy-poly(ethylene glycol)-b-poly(4-[2,2,6,6-tetramethylpiperidine-1-oxyl]oxymethylstyrene)] (MeO-PEG-b-PMOT), which is an amphiphilic block copolymer with stable nitroxide radicals in a hydrophobic segment as a side chain via an ether linkage (Fig.…”

Murine Models of Inflammatory Bowel Disease (IBD)

“…Within the damaged epithelium, neutrophils and macrophages are the most common immune cells present. Therapies that target the downstream mediators of these cells, such as reactive oxygen species, are therefore protective (Krieglstein et al 2001;Amrouche-Mekkioui and Djerdjouri 2012;Vong et al 2012;Yasukawa et al 2012). While the acute chemical-induced colitis models typically only incorporate features of innate biology (both epithelial and immune), the chronic and progressive models typically illustrate a complex interplay between innate biology and adaptive immune responses.…”

Exploiting Oxidative Microenvironments in the Body as Triggers for Drug Delivery Systems

“…For example, a novel redox nanoparticle (RNP O ) consisting of a self-assembling ampiphilic block copolymer containing a derivative of the antioxidant TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl) in the hydrophobic segment has been shown to be more effective than free TEMPOL or mesalamine (an anti-inflammatory compound) at treating colitis in mice (190).The confinement of the nitroxide radical-containing TEMPOL derivative in the hydrophobic core of RNP O nanoparticles enhanced its biocompatibility, and the nanoparticles' size (40 nm) caused them to accumulate in the colonic mucosa. A recent report described the antioxidant properties of nanoparticles (PVAX) formulated from copolyoxylate containing vanillyl alcohol (VA) (110).…”