在大鼠、狗和 IBD 患者中使用与物种无关的薄膜涂层进行结肠靶向治疗

IF 5.2 2区 医学 Q1 PHARMACOLOGY & PHARMACY
F. Ferraro , L.M. Sonnleitner , C. Neut , S. Mahieux , J. Verin , J. Siepmann , F. Siepmann
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引用次数: 0

摘要

研究发现,多糖可用于人类炎症性肠病(IBD)患者以及大鼠和狗(临床前研究中常用的动物)的结肠靶向治疗。多糖会被结肠酶(由细菌分泌)降解,引发药物在目标部位开始释放。必须指出的是,大鼠、狗和人体内的微生物群有很大不同。因此,在动物身上观察到的这种结肠靶向系统的性能可能无法预测患者的情况。本研究的目的就是要限制这种风险。在接种了 IBD 患者、健康狗和 "IBD 大鼠"(诱发结肠炎症)粪便样本的培养基中接触不同的多糖。培养基 pH 值的动态变化被用作细菌增殖的指标,因此也被用作多糖作为细菌底物的潜力的指标。在 pH 值变化的程度及其物种依赖性方面,观察到了根本性的差异。最有前途的多糖被用来制备围绕着负载 5-aminosalicilic acid (5-ASA) 的启动子核心的聚合物薄膜涂层。为了限制多糖在上消化道过早溶解/膨胀,薄膜涂层中还加入了乙基纤维素。在接种了 IBD 患者、健康狗和 "IBD 大鼠 "粪便样本的培养基中,对药物释放进行了监测。为了进行比较,还测量了纯培养基中 5-ASA 的释放情况。大多数薄膜涂层显示出高度依赖物种的药物释放动力学或有限的结肠靶向能力。有趣的是,芦荟和灵芝(一种蘑菇)的提取物在所有物种中都显示出结肠靶向的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Colon targeting in rats, dogs and IBD patients with species-independent film coatings

Colon targeting in rats, dogs and IBD patients with species-independent film coatings

Polysaccharides were identified, which allow for colon targeting in human Inflammatory Bowel Disease (IBD) patients, as well as in rats and dogs (which are frequently used as animals in preclinical studies). The polysaccharides are degraded by colonic enzymes (secreted by bacteria), triggering the onset of drug release at the target site. It has to be pointed out that the microbiota in rats, dogs and humans substantially differ. Thus, the performance of this type of colon targeting system observed in animals might not be predictive for patients. The aim of this study was to limit this risk. Different polysaccharides were exposed to culture medium inoculated with fecal samples from IBD patients, healthy dogs and “IBD rats” (in which colonic inflammation was induced). Dynamic changes in the pH of the culture medium were used as an indicator for the proliferation of the bacteria and, thus, the potential of the polysaccharides to serve as their substrate. Fundamental differences were observed with respect to the extent of the pH variations as well as their species-dependency. The most promising polysaccharides were used to prepare polymeric film coatings surrounding 5-aminosaliciylic acid (5-ASA)-loaded starter cores. To limit premature polysaccharide dissolution/swelling in the upper gastro intestinal tract, ethylcellulose was also included in the film coatings. Drug release was monitored upon exposure to culture medium inoculated with fecal samples from IBD patients, healthy dogs and “IBD rats”. For reasons of comparison, also 5-ASA release in pure culture medium was measured. Most film coatings showed highly species-dependent drug release kinetics or limited colon targeting capacity. Interestingly, extracts from aloe vera and reishi (a mushroom) showed a promising potential for colon targeting in all species.

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来源期刊
International Journal of Pharmaceutics: X
International Journal of Pharmaceutics: X Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.60
自引率
0.00%
发文量
32
审稿时长
24 days
期刊介绍: International Journal of Pharmaceutics: X offers authors with high-quality research who want to publish in a gold open access journal the opportunity to make their work immediately, permanently, and freely accessible. International Journal of Pharmaceutics: X authors will pay an article publishing charge (APC), have a choice of license options, and retain copyright. Please check the APC here. The journal is indexed in SCOPUS, PUBMED, PMC and DOAJ. The International Journal of Pharmaceutics is the second most cited journal in the "Pharmacy & Pharmacology" category out of 358 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.
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