Lam P-L, Gambari R, Kok S H-L, Lam K-H, Tang J C-O, Bian Z-X, Lee K K-H, Chui C-H
State Key Laboratory of Chirosciences, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, SAR, P.R. China.
Centre of Biotechnology, Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
Int J Mol Med. 2015 Feb;35(2):503-10. doi: 10.3892/ijmm.2014.2027. Epub 2014 Dec 8.
Aspergillus niger (A. niger) is a common species of Aspergillus molds. Cutaneous aspergillosis usually occurs in skin sites near intravenous injection and approximately 6% of cutaneous aspergillosis cases which do not involve burn or HIV-infected patients are caused by A. niger. Biomaterials and biopharmaceuticals produced from microparticle-based drug delivery systems have received much attention as microencapsulated drugs offer an improvement in therapeutic efficacy due to better human absorption. The frequently used crosslinker, glutaraldehyde, in gelatin-based microencapsulation systems is considered harmful to human beings. In order to tackle the potential risks, agarose has become an alternative polymer to be used with gelatin as wall matrix materials of microcapsules. In the present study, we report the eco-friendly use of an agarose/gelatin-based microencapsulation system to enhance the antifungal activity of gallic acid and reduce its potential cytotoxic effects towards human skin keratinocytes. We used optimal parameter combinations, such as an agarose/gelatin ratio of 1:1, a polymer/oil ratio of 1:60, a surfactant volume of 1% w/w and a stirring speed of 900 rpm. The minimum inhibitory concentration of microencapsulated gallic acid (62.5 µg/ml) was significantly improved when compared with that of the original drug (>750 µg/ml). The anti-A. niger activity of gallic acid -containing microcapsules was much stronger than that of the original drug. Following 48 h of treatment, skin cell survival was approximately 90% with agarose/gelatin microcapsules containing gallic acid, whereas cell viability was only 25-35% with free gallic acid. Our results demonstrate that agarose/gelatin-based microcapsules containing gallic acid may prove to be helpful in the treatment of A. niger-induced skin infections near intravenous injection sites.
黑曲霉是曲霉属霉菌的常见种类。皮肤曲霉病通常发生在静脉注射附近的皮肤部位，在不涉及烧伤或艾滋病毒感染患者的皮肤曲霉病病例中，约6%是由黑曲霉引起的。基于微粒的药物递送系统生产的生物材料和生物制药受到了广泛关注，因为微囊化药物由于更好的人体吸收性而提高了治疗效果。基于明胶的微囊化系统中常用的交联剂戊二醛被认为对人体有害。为了应对潜在风险，琼脂糖已成为与明胶一起用作微胶囊壁基质材料的替代聚合物。在本研究中，我们报告了一种基于琼脂糖/明胶的微囊化系统的环保用途，以增强没食子酸的抗真菌活性并降低其对人皮肤角质形成细胞的潜在细胞毒性作用。我们使用了最佳参数组合，如琼脂糖/明胶比例为1:1、聚合物/油比例为1:60、表面活性剂体积为1% w/w以及搅拌速度为900 rpm。与原药（>750 µg/ml）相比，微囊化没食子酸的最低抑菌浓度（62.5 µg/ml）有显著提高。含没食子酸微胶囊的抗黑曲霉活性比原药强得多。处理48小时后，含没食子酸的琼脂糖/明胶微胶囊处理的皮肤细胞存活率约为90%，而游离没食子酸处理的细胞活力仅为25 - 35%。我们的结果表明，含没食子酸的琼脂糖/明胶基微胶囊可能有助于治疗静脉注射部位附近由黑曲霉引起的皮肤感染。
