School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK; Faculty of Pharmacy, Philadelphia University, P.O Box 1, Amman 19392, Jordan.
Biomater Adv. 2024 Feb;157:213735. doi: 10.1016/j.bioadv.2023.213735. Epub 2023 Dec 21.
Inflammatory bowel disease (IBD) are chronic inflammatory conditions which cause significant patient morbidity. Local drug delivery to the colon can improve treatment efficacy and reduce side effects associated with IBD treatment. Smart drug delivery systems are designed to regulate the release of therapeutic agents at the desired site of action. pH-responsive drug carriers have been previously utilised for improved oral drug delivery beyond stomach harsh conditions. Additionally, the colon possesses a diverse microbiome secreting bioactive molecules e.g., enzymes, that can be exploited for targeted drug delivery. We herein synthesised and characterised a 2-hydroxyethyl methacrylate and methacrylic acid copolymer, crosslinked with an azobenzyl crosslinker, that displayed pH- and enzyme-responsive properties. The swelling and drug release from hydrogel were analysed in pH 1.2, 6.5 and 7.4 buffers, and in the presence of rat caecal matter using metronidazole and mesalamine as model BCS Class I and IV drugs, respectively. Swelling studies displayed pH-responsive swelling behaviour, where swelling was maximum at pH 7.4 and minimum at pH 1.2 (69 % versus 32 %). Consequently, drug release was limited in gastric and small intestinal conditions but increased significantly when exposed to colonic conditions containing caecal matter. This system displays promising capacity for achieving colon-targeted drug delivery with enhanced dissolution of poorly water-soluble drugs for local treatment of IBD and other colon-targeted therapies.
炎症性肠病（IBD）是慢性炎症性疾病，会导致患者出现严重的疾病负担。将药物局部递送到结肠可以提高治疗效果，并减少与 IBD 治疗相关的副作用。智能药物递送系统旨在调节治疗剂在所需作用部位的释放。已经先前利用 pH 响应性药物载体来改善口服药物递送到胃恶劣条件之外的效果。此外，结肠具有多样化的微生物群落，分泌具有生物活性的分子，例如酶，可以用于靶向药物递送。本文合成并表征了一种 2-羟乙基甲基丙烯酸酯和甲基丙烯酸共聚物，用偶氮苯交联剂交联，具有 pH 和酶响应特性。使用甲硝唑和柳氮磺胺吡啶分别作为 BCS 分类 I 和 IV 药物的模型，在 pH 1.2、6.5 和 7.4 缓冲液中和存在大鼠盲肠物质的情况下，分析了水凝胶的溶胀和药物释放。溶胀研究显示出 pH 响应性溶胀行为，在 pH 7.4 时溶胀最大，在 pH 1.2 时最小（69%对 32%）。因此，在胃和小肠条件下药物释放受到限制，但当暴露于含有盲肠物质的结肠条件下时，药物释放显著增加。该系统显示出具有实现结肠靶向药物递送的潜力，可增强局部治疗 IBD 和其他结肠靶向疗法的难溶性药物的溶解。
