Smith Riannon, Brogden Nicole, Fiegel Jennifer
Chemical and Biochemical Engineering, College of Engineering, The University of Iowa, Iowa City, Iowa, USA 52242.
Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, Iowa, USA 52242.
J Drug Deliv Sci Technol. 2023 Nov;89. doi: 10.1016/j.jddst.2023.105000. Epub 2023 Sep 28.
Topical antimicrobial treatments for severe burns and chronic wounds provide effective treatment against infections, but cause pain and discomfort with application. This study aimed to develop an antimicrobial topical formulation comprising thermoreversible poloxamers (Pluronic F127 and F68) and a broad-spectrum antimicrobial agent (ciprofloxacin hydrochloride, CH), that could be sprayed to eliminate application pain while maintaining antimicrobial activity. Formulations were characterized to determine their sprayability under cold conditions, gelation temperature, final storage modulus at skin temperature, drug release profile, permeation through impaired porcine skin, and inhibition against common bacterial pathogens that colonize wounds. All cold formulations were sprayable from simple hand-held, pump-action sprayers due to their low viscosity. Upon heating, 17 and 20% Pluronic F127 formulations produced hydrogels eight to ten degrees below skin temperature, independent of ciprofloxacin loading. Increasing concentrations of Pluronic F127 increased the final storage modulus and viscosity of the gels, while inclusion of Pluronic F68 reduced these properties, showing that hydrogel rheological properties at skin temperature can be tuned via choice of formulation. Drug release was directly correlated to the rheological properties, with stiffer gels resulting in a decrease in drug release rate. Overall, gels released about 65-90% of their load within 12 hours. skin permeation demonstrated that drug was well retained in impaired porcine skin, which is desired to continuously treat bacteria localized to the wound. A well-diffusion assay indicated that the hydrogels had greater bacterial inhibition against , , and two strains of when compared to commercial controls. Overall, the results show the potential of CH-loaded poloxamer formulations as suitable sprayable topical dressings to deliver antimicrobials directly to wounds.
用于严重烧伤和慢性伤口的局部抗菌治疗可有效对抗感染,但应用时会引起疼痛和不适。本研究旨在开发一种抗菌局部制剂,其包含热可逆泊洛沙姆(普朗尼克F127和F68)和一种广谱抗菌剂(盐酸环丙沙星,CH),该制剂可喷雾使用以消除应用时的疼痛,同时保持抗菌活性。对制剂进行了表征,以确定其在寒冷条件下的喷雾性、凝胶化温度、皮肤温度下的最终储能模量、药物释放曲线、通过受损猪皮肤的渗透情况以及对伤口定植的常见细菌病原体的抑制作用。所有冷制剂由于其低粘度,均可从简单的手持式泵动喷雾器中喷出。加热后,17%和20%普朗尼克F127制剂在低于皮肤温度8至10度时形成水凝胶,与环丙沙星负载量无关。普朗尼克F127浓度的增加会提高凝胶的最终储能模量和粘度,而加入普朗尼克F68会降低这些性质,表明可通过制剂选择来调节皮肤温度下水凝胶的流变性质。药物释放与流变性质直接相关,较硬的凝胶会导致药物释放速率降低。总体而言,凝胶在12小时内释放了约65 - 90%的负载量。皮肤渗透实验表明药物能很好地保留在受损猪皮肤中,这对于持续治疗伤口局部的细菌是有利的。一项扩散良好的检测表明,与商业对照相比,水凝胶对金黄色葡萄球菌、大肠杆菌和两种铜绿假单胞菌菌株具有更强的细菌抑制作用。总体而言,结果表明负载CH的泊洛沙姆制剂有潜力作为合适的可喷雾局部敷料,将抗菌剂直接递送至伤口。