Sun Peng, Wang Zheng, Wu Tong, Zuo Shishuai, Huang Xiaoyu, Cui Zilian, Zhang Dong
Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Department of Chemotherapy, Shandong Second Provincial General Hospital, Shandong Provincial ENT Hospital, Jinan, China.
Front Bioeng Biotechnol. 2022 Jun 27;10:906835. doi: 10.3389/fbioe.2022.906835. eCollection 2022.
The aim of this study was to prepare injectable, adhesive, and self-healing composite hydrogels loaded with oxybutynin hydrochloride and verify its function in the treatment of overactive bladder. The ultraviolet (UV) absorption of oxybutynin (Oxy) in the solution was detected using a UV spectrophotometer at 233 nm, and the cumulative drug release was calculated using Origin software. L929 mouse fibroblasts were used to test cell adhesion to OCP50 and OCP100 hydrogels. Both FT-IR and NMR overactive bladder demonstrated that Dex was oxidized to PDA with aldehyde groups. Urodynamic examinations were performed 24 h after intraperitoneal injection in the rat model. The relative expression levels of Orai1 and STIM1 were detected by western blot (WB) and QPCR. After loading Oxy, the shear adhesion under the wet conditions of OCP50 and OCP100 was higher than CP50 and CP100 ( < 0.05), and both were suitable for intravaginal administration. After 72 h of release, oxybutynin released 82.8% in OCP100 hydrogel and 70% in OCP50. Compared to the model, OCP50, CP100, and OCP100 relieved the overactive bladder and inhibited the expression of Orail and STIM1. Oxybutynin hydrogel could provide relief to overactive bladder by decreasing the expression of Orail and STIM1 in rats.
本研究的目的是制备负载盐酸奥昔布宁的可注射、可黏附且可自愈的复合水凝胶，并验证其在治疗膀胱过度活动症中的作用。使用紫外可见分光光度计在233nm处检测溶液中奥昔布宁（Oxy）的紫外吸收，并使用Origin软件计算药物累积释放量。使用L929小鼠成纤维细胞测试细胞对OCP50和OCP100水凝胶的黏附情况。傅里叶变换红外光谱（FT-IR）和核磁共振（NMR）均表明膀胱过度活动症中右旋糖酐被氧化为带有醛基的聚多巴胺（PDA）。在大鼠模型腹腔注射24小时后进行尿动力学检查。通过蛋白质免疫印迹法（WB）和定量聚合酶链反应（QPCR）检测Orai1和基质相互作用分子1（STIM1）的相对表达水平。负载奥昔布宁后，OCP50和OCP100在湿态下的剪切黏附力高于CP50和CP100（P<0.05），两者均适用于阴道给药。释放72小时后，奥昔布宁在OCP100水凝胶中的释放率为82.8%，在OCP50中的释放率为70%。与模型组相比，OCP50、CP100和OCP100缓解了膀胱过度活动症并抑制了Orail和STIM1的表达。奥昔布宁水凝胶可通过降低大鼠中Orail和STIM1的表达来缓解膀胱过度活动症。
