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投稿时间:2021-12-07 网络发布日期:2022-06-20
投稿时间:2021-12-07 网络发布日期:2022-06-20
中文摘要: 目的 探讨新型锂皂石/甘油磷酸钠复合纳米凝胶应用于黏膜下注射剂的可行性、有效性及安全性。方法 0.3%甘油磷酸钠粉末与不同体积的锂皂石粉末预先混合后加入纯水,合成不同浓度的水凝胶,观察其微观形态并测定其降解率和流变性能。在新鲜离体猪胃黏膜下注射2 ml生理盐水、0.4%透明质酸钠与不同浓度(2%~5%)水凝胶,观察胃黏膜隆起高度随时间的变化;注射相同面积后模拟内镜下黏膜下剥离术(ESD)进行电刀剥离,记录完整剥离的时间。并用CCK8法检测5%水凝胶浸提液对胃黏膜GES-1细胞存活率的影响。结果 各项表征实验表明,合成的水凝胶呈多孔结构,性质稳定,具备剪切变稀的能力,且随着锂皂石浓度提高,成胶速度更快。体外黏膜下隆起实验中,在90 min时生理盐水组隆起高度的维持率不足50%,0.4%透明质酸钠组约为55%,而2%~5%水凝胶组为68%~91%,差异具有统计学意义(P<0.05)。模拟ESD剥离平均时间也较对照组更短,差异具有统计学意义(P<0.05)。细胞毒性试验中,在加入5%水凝胶浸提液后的1~3 d内GES-1细胞活力与对照组无明显差异(P>0.05)。结论 锂皂石/甘油磷酸钠复合纳米凝胶配制简便,拥有剪切变稀的性质,在黏膜下可持久维持理想的隆起高度,且生物相容性好,有望成为一种新型的黏膜下注射剂。
Abstract:Objective To investigate the feasibility, effectiveness and safety of a new type of nanocomposite gel of laponite and sodium glycerophosphate (GP). Methods The 0.3% GP powder was mixed with different volume of laponite powder before mixing with pure water to synthesize different concentrations (2% to 5%) of hydrogel. The morphology of the hydrogel was observed and its degradation rate and rheological property were determined. And 2 ml of normal saline, 0.4% sodium hyaluronate and different concentrations of hydrogel were injected into the submucosa of freshly isolated pig stomach to observe the changes of gastric mucosal eminence height with time. After injection of the same area, electrosurgical dissection was performed by simulating endoscopic submucosal dissection (ESD), and the time of complete dissection was recorded. The effect of 5% hydrogel extract on the survival rate of GES-1 cells in gastric mucosa was detected by CCK8. Results The characterization experiments showed that the synthesized hydrogel had porous structure, stable property and shear thinning ability, and the gelation rate was faster with the increase of the concentration of laponite. In vitro submucosal eminence test, at 90 min, the eminence height maintenance rate was less than 50% in normal saline, about 55% in 0.4% sodium hyaluronate, and about 68%-91% in the 2%-5% hydrogel group, the difference was significant (P<0.05). The average time of simulated ESD stripping was also shorter than that of the control group without significant difference (P<0.05). In the cytotoxicity test, GES-1 activity in the 1-3 d after adding 5% hydrogel extract was not significantly different from that in the control group (P>0.05). Conclusion The nanocomposite gel of laponite and GP is simple, which has shear thinning property, and it can maintain ideal uplift height under the submucosal condition with good biocompatibility. It is expected to become a new submucosal injection.
keywords: Laponite Sodium glycerophosphate Nanogels Shear thinning Hydrogel Submucosal injection Endoscopic submucosal dissection
文章编号: 中图分类号:R57 R735 文献标志码:A
基金项目:国家自然科学基金(82000621)
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引用文本:
陶雨文,范文涛,赵黎黎,等.锂皂石复合水凝胶应用于内镜黏膜下注射的研究[J].中国临床研究,2022,35(6):741-746.
陶雨文,范文涛,赵黎黎,等.锂皂石复合水凝胶应用于内镜黏膜下注射的研究[J].中国临床研究,2022,35(6):741-746.