Department of Drug Delivery Research, Hoshi University, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Int J Mol Sci. 2020 Mar 30;21(7):2376. doi: 10.3390/ijms21072376.
Recently, the potential of nanoparticles (NPs) in ulcerative colitis (UC) therapy has been increasingly demonstrated. Namely, anionic NPs have been found to be accumulated efficiently to the UC damaged area due to epithelial enhanced permeability and retention (eEPR) effect. Previously, a novel anionic nanogel system (NG(S)) was prepared, and evaluated for the efficacy and toxicity. In the present study, release behaviors and biodistribution were investigated in detail to elucidate the functional mechanisms. Rats with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis (UC) were used as biomodels. In vitro release was examined with or without the contents of the cecum or distal colon. Gastrointestinal distribution and plasma concentrations were investigated after the intragastric administration of 10 mg prednisolone (PD) eq./kg. At pH 1.2 and 6.8, release behaviors were slow, but controlled. Overall release was not markedly different irrespective of coexistence of intestinal contents. In in vivo studies, a large amount of PD was distributed in the lower parts of the gastrointestinal tract 6 and 12 h after administration with NG(S). PD accumulated well in the colonic parts, and prolonged release was noted. The systemic absorption of PD with NG(S) was hardly found. NG(S) concentrated the drug in the colon and showed controlled release. These behaviors were considered to lead to the previously reported good results, promotion of effectiveness and suppression of toxic side effects.
近年来，纳米粒子（NPs）在溃疡性结肠炎（UC）治疗中的潜力得到了越来越多的证明。具体来说，由于上皮细胞增强的通透性和保留（eEPR）效应，阴离子 NPs 已被发现能够有效地积累到 UC 受损区域。此前，已经制备了一种新型的阴离子纳米凝胶系统（NG(S)），并对其疗效和毒性进行了评估。在本研究中，详细研究了释放行为和体内分布，以阐明其功能机制。采用 2,4,6-三硝基苯磺酸（TNBS）诱导的溃疡性结肠炎（UC）大鼠作为生物模型。在有无盲肠或远端结肠内容物的情况下进行了体外释放研究。在给予 10mg 泼尼松龙（PD）eq/kg 后，研究了胃肠道分布和血浆浓度。在 pH 1.2 和 6.8 时，释放行为缓慢，但受到控制。无论是否存在肠道内容物，总体释放没有明显差异。在体内研究中，NG(S)给药 6 和 12 小时后，大量 PD 分布在胃肠道的下部。PD 在结肠部位蓄积良好，并观察到延长释放。NG(S) 对 PD 的全身吸收几乎没有发现。NG(S) 将药物浓缩在结肠中并显示出控制释放。这些行为被认为导致了之前报道的良好结果，即提高了疗效并抑制了毒副作用。
