Faculty of Pharmacy, University of Lahore, Lahore, 56400, Pakistan.
Pharmaceutical and Molecular Biotechnology Research Centre (PMBRC), Department of Science, South East Technological University (SETU), Waterford, X91 K0EK, Ireland.
AAPS PharmSciTech. 2024 Sep 5;25(7):204. doi: 10.1208/s12249-024-02916-5.
Benign hyperplasia (BHP) is a common disorder that affects men over the age of 60 years. Transurethral resection of the prostate (TURP) is the gold standard for operative treatment, but a range of drugs are also available to improve quality of life and to reduce BHP-associated urinary tract infections and complications. Darifenacin, an anti-muscarinic agent, has been found effective for relieving symptoms of overactive bladder associated with BHP, but the drug has poor solubility and bioavailability, which are major challenges in product development. An inorganic/organic bio-composite with gastric pH-resistant property was synthesized for the targeted oral delivery of Darifenacin to the lower gastrointestinal tract (GIT). This development was accomplished through co-precipitation of calcium carbonate in quince seed-based mucilage. The FTIR, XRD, DSC, and TGA results showed good drug-polymer compatibility, and the SEM images showed calcite formation in the quince hydrogel system. After 72 h, the drug release of 34% and 75% were observed in acidic (0.1N HCl) and 6.8 pH phosphate buffer, respectively. A restricted/less drug was permeated through gastric membrane (21.8%) as compared to permeation through intestinal membrane (65%.) The developed composite showed significant reduction in testosterone-induced prostatic hyperplasia (2.39 ± 0.12***) as compared to untreated diseased animal group. No sign of organ toxicity was observed against all the developed composites. In this study, we developed an inorganic-organic composite system that is highly biocompatible and effective for targeting the lower GIT, thereby avoiding the first-pass metabolism of darifenacin.
良性前列腺增生(BHP)是一种常见的疾病,影响 60 岁以上的男性。经尿道前列腺切除术(TURP)是手术治疗的金标准,但也有一系列药物可用于改善生活质量,并减少 BHP 相关的尿路感染和并发症。达非那新是一种抗毒蕈碱药物,已被发现可有效缓解与 BHP 相关的膀胱过度活动症的症状,但该药物的溶解度和生物利用度较差,这是产品开发的主要挑战。本研究合成了一种具有胃 pH 抗性的无机/有机生物复合材料,用于达非那新在下消化道(GIT)的靶向口服递送。这一发展是通过在榅桲种子胶中共同沉淀碳酸钙来实现的。FTIR、XRD、DSC 和 TGA 结果表明药物与聚合物具有良好的相容性,SEM 图像显示在榅桲水凝胶系统中形成了方解石。在 72 小时后,分别在酸性(0.1N HCl)和 6.8 pH 磷酸盐缓冲液中观察到 34%和 75%的药物释放。与通过肠膜的渗透(65%)相比,通过胃膜的渗透(21.8%)限制了/减少了药物的渗透。与未治疗的患病动物组相比,所开发的复合材料显著减少了睾酮诱导的前列腺增生(2.39±0.12***)。对所有开发的复合材料均未观察到器官毒性的迹象。在这项研究中,我们开发了一种高度生物相容的无机-有机复合材料系统,该系统可有效靶向下 GIT,从而避免达非那新的首过代谢。
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