银磺胺嘧啶纳米混悬剂联合温敏水凝胶：一种有效的动物模型创面愈合抗菌治疗方法。
Combined Silver Sulfadiazine Nanosuspension with Thermosensitive Hydrogel: An Effective Antibacterial Treatment for Wound Healing in an Animal Model.
机构信息
Department of Pharmacy, Shenzhen Children's Hospital, Shenzhen, Guangdong Province, 518026, People's Republic of China.
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing, 100850, People's Republic of China.
出版信息
Int J Nanomedicine. 2023 Feb 11;18:679-691. doi: 10.2147/IJN.S395004. eCollection 2023.
INTRODUCTION
Silver sulfadiazine (AgSD) is widely used in burn wound treatment due to its broad-spectrum antibacterial activity. However, its application in wound healing is greatly hindered by the low solubility of AgSD particles and their cellular cytotoxicity. Herein, we studied the safety and in vivo efficacy of nano-sized silver sulfadiazine loaded in poloxamer thermosensitive hydrogel (NS/Gel).
METHODS
In NS/Gel, silver sulfadiazine was prepared into silver sulfadiazine nanosuspension (NS) to improve the solubility and enhance its antibacterial activity, whereas the poloxamer thermosensitive hydrogel was selected as a drug carrier of NS to achieve slow drug release and reduced cytotoxicity. The acute toxicity of silver sulfadiazine nanosuspension was first evaluated in healthy mice, and its median lethal dose (LD) was calculated by the modified Karber method. Furthermore, in vivo antibacterial effect and wound healing property of NS/Gel were evaluated on the infected deep second-degree burn wound mice model.
RESULTS
The mortality ratio of mice was concentration-dependent, and the LD for silver sulfadiazine nanosuspension was estimated to be 252.1 mg/kg (230.8 to 275.4 mg/kg, 95% confidence limit). The in vivo dosages used for burn wound treatment (40-50 mg/kg) were far below LD (252.1 mg/kg). NS/Gel significantly accelerated wound healing in the deep second wound infection mice model, achieving > 85% wound contraction on day 14. in the wound region was eradicated after 7 days in NS/Gel group, while the bacterial colony count was still measurable in the control group. Histological analysis and cytokines measurement confirmed that the mice treated with NS/Gel exhibited well-organized epithelium and multiple keratinized cell layers compared to control groups with the modulated expression of IL-6, VEGF, and TGF-β.
CONCLUSION
The combination of silver sulfadiazine nanosuspension and thermo-responsive hydrogel has great potential in clinical burn wound treatment.
简介
磺胺嘧啶银（AgSD）由于其广谱抗菌活性而被广泛用于烧伤创面治疗。然而，其在伤口愈合中的应用受到 AgSD 颗粒低溶解度及其细胞毒性的极大阻碍。在此，我们研究了载纳米磺胺嘧啶银的泊洛沙姆热敏水凝胶（NS/Gel）的安全性和体内疗效。
方法
在 NS/Gel 中，磺胺嘧啶银被制备成磺胺嘧啶银纳米混悬剂（NS）以提高其溶解度并增强其抗菌活性，而泊洛沙姆热敏水凝胶则被选作 NS 的药物载体以实现药物缓慢释放和降低细胞毒性。首先在健康小鼠中评价磺胺嘧啶银纳米混悬剂的急性毒性，并用改良 Karber 法计算其半数致死量（LD）。此外，还在感染深二度烧伤创面模型的小鼠中评价了 NS/Gel 的体内抗菌作用和创面愈合特性。
结果
小鼠的死亡率与浓度呈依赖性，磺胺嘧啶银纳米混悬剂的 LD 估计为 252.1 mg/kg（230.8 至 275.4 mg/kg，95%置信限）。用于烧伤创面治疗的体内剂量（40-50 mg/kg）远低于 LD（252.1 mg/kg）。NS/Gel 显著加速了深二度创面感染模型中的创面愈合，在第 14 天达到了>85%的创面收缩。在 NS/Gel 组中，第 7 天创面区域的细菌被完全清除，而对照组中仍可检测到细菌菌落。组织学分析和细胞因子测量证实，与对照组相比，接受 NS/Gel 治疗的小鼠表现出组织有序的上皮和多个角化细胞层，并且 IL-6、VEGF 和 TGF-β的表达也得到了调节。
结论
磺胺嘧啶银纳米混悬剂与温敏水凝胶的结合在临床烧伤创面治疗中有很大的应用潜力。
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