小岛
活力测定
胆红素
泊洛沙姆
化学
移植
胰岛
男科
内分泌学
药理学
内科学
医学
胰岛素
生物化学
体外
有机化学
聚合物
共聚物
作者
Bronwyn Anne Fullagar,Wei Rao,Chen Gilor,Feng Xu,Xiaoming He,Christopher A. Adin
标识
DOI:10.1177/0963689717735112
摘要
Pancreatic islet transplantation is the only curative, noninvasive treatment for type 1 diabetes mellitus; however, high rates of cell death in the immediate postimplantation period have limited the success of this procedure. Bilirubin, an endogenous antioxidant, can improve the survival of murine pancreatic allografts during hypoxic stress but has poor solubility in aqueous solutions. We hypothesized that nano-encapsulation of bilirubin in pluronic 127-chitosan nanoparticle bilirubin (nBR) would improve uptake by murine pancreatic islet cells and improve their viability following hypoxic stress. Nano-bilirubin was synthesized, and drug release characteristics were studied in vitro. Cellular uptake of nBR was compared to free bilirubin (fBR) in an insulinoma cell line (INS-R3) model using confocal-like structured illumination microscopy. Next, C57BL/6 mouse islets were treated with concentrations of 0 to 20 μM of nBR, fBR, or empty nanoparticle (eNP), prior to incubation under standard or hypoxic conditions. Islet viability and function were compared between treatment groups. Release of bilirubin was greatest from nBR suspended in protein-rich solution. Increased, selective uptake of nBR by INS-R3 cells was demonstrated. Cell death after hypoxic stress was significantly decreased in murine islets treated with 5 μM nBR (18.5% ± 14.1) compared to untreated islets (33.5% ± 17.5%; P = 0.019), with reduction in central necrosis. Treatment group had a significant effect on glucose stimulation index [SI], ( P = 0.0137) and islets treated with 5 μM nBR had the highest SI overall. Delivery of bilirubin using pluronic F127-chitosan NP improves uptake by murine islets compared to fBR and offers dose-dependent protective effects following hypoxic stress.
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