Preparation and in vitro evaluation of Vancomycin loaded Montmorillonite-Sodium Alginate topical gel for wound infection

Abstract Despite decades of research, wound healing remains a significant public health problem. This study aimed to develop and evaluate a topical sodium alginate gel containing vancomycin (Van) loaded MMT NPs for wound healing applications. Van was loaded in MMT at different conditions (pHs of 6, 7 and temperatures of 40, 50 °C) (Van/MMT NPs). The optimum formulation (with the smallest particle size and a high value of zeta potential; 270.8 ± 77.35 nm and -35.96 ± 2.73, respectively) showed a high drug-loading capacity (entrapment efficacy of 96%) and a sustained release pattern of Van (95%) over 480 min. The optimum Van/MMT NPs were embedded into the sodium alginate (SA) gel (Van/MMT NPs/SA gel). The Van/ MMT NPs/SA gel showed a sustained and slow release pattern of Van (95%) over 50 h. FTIR tests revealed the electrostatic interaction between MMT and Van. The broth macrodilution tube method was used to determine the minimum inhibitory concentration (MIC) of Van, Van/ MMT NPs, and Van/MMT NPs/SA gel against Staphylococcus aureus. The results showed the promising antibacterial activity of Van/MMT NPs/SA gel, thus, this gel can be a promising formulation for the management of infected wounds.

摘要 尽管已有数十年的研究积累，伤口愈合仍是一项亟待解决的重大公共卫生问题。本研究旨在开发并评估一种负载万古霉素（Vancomycin，Van）的蒙脱石（Montmorillonite，MMT）纳米粒（Nanoparticles，NPs）外用海藻酸钠（sodium alginate，SA）凝胶，用于伤口愈合领域。
研究在不同条件下（pH值6、7，温度40℃、50℃）将万古霉素负载于蒙脱石载体中，制备得到万古霉素-蒙脱石纳米粒（Van/MMT NPs）。筛选得到的最优配方具备最小粒径与较高的zeta电位（zeta potential），分别为270.8 ± 77.35 nm与-35.96 ± 2.73，同时拥有较高的载药量（drug-loading capacity）与96%的包封率（entrapment efficacy），且可在480分钟内实现万古霉素95%的持续释放。
将该最优万古霉素-蒙脱石纳米粒嵌入海藻酸钠凝胶基质中，制得万古霉素-蒙脱石纳米粒/海藻酸钠凝胶（Van/MMT NPs/SA gel）。该复合凝胶可在50小时内实现万古霉素95%的持续缓释。傅里叶变换红外光谱（Fourier Transform Infrared Spectroscopy，FTIR）测试结果证实，蒙脱石与万古霉素之间存在静电相互作用。
采用肉汤宏观稀释试管法（broth macrodilution tube method）测定万古霉素、万古霉素-蒙脱石纳米粒以及万古霉素-蒙脱石纳米粒/海藻酸钠凝胶对金黄色葡萄球菌（Staphylococcus aureus）的最低抑菌浓度（minimum inhibitory concentration，MIC）。结果显示，万古霉素-蒙脱石纳米粒/海藻酸钠凝胶具备优异的抗菌活性，因此该凝胶有望成为感染性伤口临床管理的理想候选制剂。