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研制更为高效舒适、满足患者需求的伤口敷料一直是医疗器械领域的研究热点。针对目前商品化液体敷料通常为水制剂，粘附性不足且成分较为单一的问题，本论文提出用颗粒稳定的Pickering乳液制备新型敷料，可以通过组分的选择和亲疏水药物的装载实现优异的促愈性能。同时，Pickering乳液具有剪切变稀特性，在具备高粘度的同时还可实现喷雾给药。此外，Pickering乳液避免了传统乳液中表面活性剂相关的溶血、刺激反应及毒副作用。论文的主要研究结果如下：1. 以壳聚糖为原料，用沉淀法制备得到粒径在300 - 600 nm间的分散性良好、粒径均一的纳米颗粒。以该壳聚糖纳米颗粒为水相稳定剂，植物精油为油相，在油相内装载姜黄素，通过考察油相种类、颗粒浓度、油水相体积比及水相种类，筛选得到最优制备条件为：以装载姜黄素的茶树油为油相，油水相体积比为1：9，颗粒浓度为4 mg/mL，成功制备得到了粒径为2 μm左右的稳定的Pickering乳液。流变性能测定结果表明该Pickering乳液具有高粘度与剪切变稀特性。稳定性实验表明其具有良好的储存稳定性。2. 体内外抑菌实验表明该Pickering乳液对伤口感染中常见的革兰氏阴性大肠杆菌（E.coli）、革兰氏阳性金黄色葡萄球菌（S.aureus）及革兰氏阳性耐甲氧西林金黄色葡萄球菌（MRSA）具有优异的抑菌效果。HSF人表皮成纤维细胞实验表明该Pickering乳液具有良好的生物相容性，且对成纤维细胞增殖有一定的促进效果。动物实验结果表明该Pickering乳液能显著促进小鼠伤口愈合。3. 细菌生物膜渗透实验表明该Pickering乳液对细菌生物膜具有良好的渗透性，有望用于治疗细菌生物膜相关的慢性伤口感染。综上，本研究制备了基于壳聚糖纳米颗粒、植物精油及姜黄素的Pickering乳液，该Pickering乳液具有高静态粘度、可喷雾给药、高效抗菌且具有良好的促愈性能，是一种应用前景好的伤口敷料，并为液体敷料的研制提供了新思路。;Developing more effective and comfortable wound dressings is always one of the hot topic in the field of medical instruments. At present, commercial liquid dressings are usually aqueous formulation with poor adhesion and have relatively limited ingredients. To address these problems, a particle-stabilized Pickering emulsion was formulated as a novel wound dressing in this work. Pickering emulsions could achieve excellent healing effects by selecting components and being loaded with hydrophilic or hydrophobic drugs. Meanwhile, Pickering emulsion had shear thinning behaviour, which allowed it to spray while having high viscosity. Furthermore, Pickering emulsion avoided hemolysis, irritation and toxicity related to surfactants. The main results of the thesis are as follows:1. Chitosan nanoparticles around 300 - 600 nm were prepared successfully by precipitation. Pickering emulsion was prepared by using these nanoparticles as stabilizer and using five different plant essential oils as oil phase. Meanwhile, the oil phase was loaded with curcumin. The Pickering emulsion was prepared by adjusting the type of oil phase, the concentration of chitosan nanoparticles, the oil-water ratio and the type of water phase. Finally, the stable Pickering emulsion with a diameter around 2 μm was obtained by using chitosan nanoparticles with a concentration of 4 mg/mL and tea tree oil containing curcumin. The rheological property measurement showed that the Pickering emulsion had high viscosity and shear thinning behaviour. The stability experiment revealed that the Pickering emulsion had good storage stability.2. The antibacterial experiments in vivo and in vitro showed that the Pickering emulsion had the excellent antibacterial activity towards the Gram-negative Escherichia coli (E. coli), Gram-positive Staphylococcus aureus (S. aureus) and Gram-positive methicillin-resistant Staphylococcus aureus (MRSA). The cell test showed that the Pickering emulsion had good biosafety and could promote the growth of the fibroblasts. Moreover, the animal experiment revealed that the Pickering emulsion could significantly promote the process of wound healing.3. The results of the bacterial biofilms penetration experiment revealed that the Pickering emulsion could effectively penetrate the bacterial bioﬁlms. This indicated that the Pickering emulsion had promising prospects for the treatment of persistent infections of chronic wounds associated with bacterial biofilms.In summary, this study prepared a Pickering emulsion based on chitosan nanoparticles, plant essential oils and curcumin. The results showed that this sprayed Pickering emulsion had high static viscosity, high antibacterial activity and good healing effects. All the results indicated that Pickering emulsion is a promising candidate for wound dressings and could provide new ideas for the development of liquid dressings.
|包谢茹. 伤口促愈Pickering乳液的制备与应用[D]. 中国科学院大学,2020.|
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