Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA)-CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, 5000, Córdoba, Argentina.
Farmacia Central, Hospital Nacional de Clínicas, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Drug Deliv Transl Res. 2018 Oct;8(5):1000-1013. doi: 10.1007/s13346-018-0523-7.
The purpose of this work was to develop an effective carbomer hydrogel to be used to treat second-degree burns that combined ciprofloxacin and lidocaine (CbCipLid hydrogel). Its antibiotic and anesthetic efficacy and the physical and chemical properties of the CbCipLid hydrogel (release rate and kinetics, rheology, appearance, and drug content) were evaluated both before and after a sterilization cycle and also after 6 months of storage. For the in vivo studies, second-degree burns were developed in a rat model. Animals were divided into three groups: CbCipLid hydrogel, silver sulfadiazine cream (reference), and carbomer hydrogel (as control). The treatments were applied daily for 21 days, and the healing was monitored by macroscopic observation and histologic evaluation. The anesthetic effect was evaluated through the corneal touch threshold in a rabbit eye model. The CbCipLid hydrogel obtained is transparent and allows the loading of ciprofloxacin above its solubility at a neutral pH, with a rheology which is convenient for topical administration. Its physical and chemical properties remained unchanged after sterilization and for at least six additional months. Both ciprofloxacin and lidocaine are reversibly released from the CbCipLid hydrogel with a kinetics fitting the Higuchi model. The presence of a biologic-like fluid increased the rate of drug delivery through an ionic exchange mechanism. Treatment with the CbCipLid hydrogel decreased the wound-healing period, compared with the reference, and was associated with a greater number of fibroblasts and a faster rate of epithelialization and dermis reconstruction. These differences were assigned to the moist environment provided by the hydrogel and also to the presence of a therapeutic concentration of ciprofloxacin. Moreover, CbCipLid hydrogel provides an immediate anesthetic effect, which is significantly more intense than that of the reference. Based on these results, it is believed that the CbCipLid hydrogel could be a potential candidate in the prophylaxis/treatment of second-degree burns.
本工作旨在开发一种有效的卡波姆水凝胶，用于治疗合并环丙沙星和利多卡因的二度烧伤（CbCipLid 水凝胶）。对 CbCipLid 水凝胶（释放率和动力学、流变学、外观和药物含量）进行了杀菌循环前后以及 6 个月储存后的物理化学性质、抗生素和麻醉效果评估。在体内研究中，在大鼠模型中建立了二度烧伤。动物分为三组：CbCipLid 水凝胶、磺胺嘧啶银乳膏（对照）和卡波姆水凝胶（对照）。每日治疗 21 天，并通过宏观观察和组织学评估监测愈合情况。通过兔眼角膜触阈值评估麻醉效果。获得的 CbCipLid 水凝胶透明，可在中性 pH 值下负载高于其溶解度的环丙沙星，流变学方便于局部给药。其物理化学性质在杀菌后至少 6 个月内保持不变。环丙沙星和利多卡因均从 CbCipLid 水凝胶中可逆释放，动力学符合 Higuchi 模型。生物类似物流体的存在通过离子交换机制增加了药物的传递速度。与对照相比，CbCipLid 水凝胶治疗可缩短创面愈合时间，且与更多的成纤维细胞、更快的上皮化和真皮重建速度相关。这些差异归因于水凝胶提供的湿润环境以及存在治疗浓度的环丙沙星。此外，CbCipLid 水凝胶可提供即时麻醉效果，其强度明显强于对照。基于这些结果，相信 CbCipLid 水凝胶可能是预防/治疗二度烧伤的潜在候选药物。
