Jadach Barbara, Nowak Agata, Długaszewska Jolanta, Kordyl Oliwia, Budnik Irena, Osmałek Tomasz
Division of Industrial Pharmacy, Chair and Department of Pharmaceutical Technology, Poznan University of Medical Sciences, 3 Rokietnicka, 60-806 Poznan, Poland.
Chair and Department of Pharmaceutical Technology, Poznan University of Medical Sciences, 3 Rokietnicka, 60-806 Poznan, Poland.
Gels. 2024 Apr 15;10(4):264. doi: 10.3390/gels10040264.
Mycoses of the skin are infectious diseases caused by fungal microorganisms that are generally treated with topical agents. However, such therapy is often ineffective and has to be supported by oral use of active substances, which, in turn, can cause many side effects. A good alternative for the treatment of deep-skin mycoses seems to be microneedles (MNs). The aim of this research was to fabricate and evaluate the properties of innovative MNs coated with a hydrogel as potential carriers for clotrimazole (CLO) in the treatment of deep fungal skin infections. A 3D printing technique using a photo-curable resin was employed to produce MNs, which were coated with hydrogels using a dip-coating method. Hydrogels were prepared with carbopol EZ-3 Polymer (Lubrizol) in addition to glycerol and triisopropanolamine. Clotrimazole was introduced into the gel as the solution in ethanol or was suspended. In the first step of the investigation, a texture analysis of hydrogels was prepared with a texture analyzer, and the drug release studies were conducted with the use of automatic Franz diffusion cells. Next, the release profiles of CLO for coated MNs were checked. The last part of the investigation was the evaluation of the antifungal activity of the prepared systems, and the inhibition of the growth of was checked with the diffusion and suspended-plate methods. The texture profile analysis (TPA) for the tested hydrogels showed that the addition of ethanol significantly affects the following studied parameters: hardness, adhesiveness and gumminess, causing a decrease in their values. On the other hand, for the gels with suspended CLO, better spreadability was seen compared to gels with dissolved CLO. The presence of the active substance did not significantly affect the values of the tested parameters. In the dissolution study, the results showed that higher amounts of CLO were released for MNs coated with a hydrogel containing dissolved CLO. Also, microbiological tests proved its efficacy against fungal cultures. Qualitative tests carried out using the diffusion method showed that circular zones of inhibition of fungal growth on the plate were obtained, confirming the hypothesis of effectiveness. The suspension-plate technique confirmed the inhibitory effect of applied CLO on the growth of . From the analysis of the data, the MNs coated with CLO dissolved in hydrogel showed better antifungal activity. All received results seem to be helpful in developing further studies for MNs as carriers of antifungal substances.
皮肤真菌病是由真菌微生物引起的传染病，通常用外用药物治疗。然而，这种治疗方法往往无效，必须辅以口服活性物质，但这反过来又会引起许多副作用。微针似乎是治疗深部皮肤真菌病的一个很好的替代方法。本研究的目的是制备和评估涂覆有水凝胶的创新微针的性能，作为克霉唑（CLO）治疗深部真菌性皮肤感染的潜在载体。采用光固化树脂的3D打印技术制备微针，并采用浸涂法将水凝胶涂覆在微针上。除甘油和三异丙醇胺外，用水性丙烯酸聚合物（路博润公司生产）制备水凝胶。克霉唑以乙醇溶液的形式引入凝胶中或进行悬浮。在研究的第一步，用质地分析仪对水凝胶进行质地分析，并使用自动弗兰兹扩散池进行药物释放研究。接下来，检查涂覆微针的CLO释放曲线。研究的最后一部分是评估所制备体系的抗真菌活性，并用扩散法和悬液平板法检查对其生长的抑制作用。对测试水凝胶的质地剖面分析（TPA）表明，添加乙醇会显著影响以下研究参数：硬度、粘附性和黏性，导致其值降低。另一方面，对于悬浮有CLO的凝胶，与溶解有CLO的凝胶相比，其铺展性更好。活性物质的存在对测试参数的值没有显著影响。在溶出度研究中，结果表明，对于涂覆有含有溶解CLO的水凝胶的微针，释放出的CLO量更高。此外，微生物测试证明了其对真菌培养物的有效性。使用扩散法进行的定性测试表明，在平板上获得了抑制真菌生长的圆形区域，证实了有效性的假设。悬液平板技术证实了所应用的CLO对其生长的抑制作用。从数据分析来看，涂覆有溶解在水凝胶中的CLO的微针显示出更好的抗真菌活性。所有得到的结果似乎有助于进一步开展微针作为抗真菌物质载体的研究。
