Abdallah Marwa H, Elghamry Hanaa A, Khalifa Nasrin E, Khojali Weam M A, Khafagy El-Sayed, Shawky Seham, El-Horany Hemat El-Sayed, El-Housiny Shaimaa
Department of Pharmaceutics, College of Pharmacy, University of Ha'il, Ha'il 81442, Saudi Arabia.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
Gels. 2023 Feb 6;9(2):137. doi: 10.3390/gels9020137.
Erythromycin (EM) is a macrolide antibiotic that is frequently used to treat skin bacterial infections. It has a short half-life (1-1.5 h), instability in stomach pH, and a low oral bioavailability. These foregoing factors limit its oral application; therefore, the development of topical formulations loaded with erythromycin is an essential point to maximize the drug's concentration at the skin. Accordingly, the current study's goal was to boost the antimicrobial activity of EM by utilizing the advantages of natural oils such as cinnamon oil. Erythromycin-loaded transethosomes (EM-TE) were generated and optimized using a Box-Behnken design employing, phospholipid concentration (A), surfactant concentration (B), and ethanol content (C) as independent variables. Their effects on entrapment efficiency, EE, (Y) and the total amount of erythromycin that penetrated the skin after 6 h, Q6h (Y), were assessed. The optimized transethosome showed a particle size of 256.2 nm, EE of 67.96 ± 0.59%, and Q6h of 665.96 ± 5.87 (µg/cm) after 6 h. The TEM analysis revealed that, the vesicles are well-known packed structures with a spherical shape. The optimized transethosomes formulation was further transformed into a cinnamon oil-based emulgel system using HPMC as a gelling agent. The generated EM-TE-emulgel was characterized by its physical features, in vitro, ex vivo studies, and antimicrobial activities. The formulation showed sufficient characteristics for effective topical application, and demonstrated a great stability. Additionally, EM-TE-Emulgel had the highest transdermal flux (120.19 μg/cm·h), and showed considerably ( < 0.05) greater antimicrobial activity, than EM-TE-gel and placebo TE-Emulgel. The action of EM was subsequently augmented with cinnamon oil, which eventually showed a notable effect against bacterial growth. Finally, these results demonstrate that the transethosomes-loaded cinnamon oil-based emulgel is an alternative way to deliver erythromycin for the treatment of topical bacterial infections.
红霉素（EM）是一种大环内酯类抗生素，常用于治疗皮肤细菌感染。它的半衰期较短（1 - 1.5小时），在胃酸环境中不稳定，口服生物利用度低。上述因素限制了其口服应用；因此，开发负载红霉素的局部制剂是使药物在皮肤处达到最大浓度的关键。相应地，本研究的目标是利用肉桂油等天然油的优势来增强红霉素的抗菌活性。采用Box - Behnken设计，以磷脂浓度（A）、表面活性剂浓度（B）和乙醇含量（C）作为自变量，制备并优化了负载红霉素的传递体（EM - TE）。评估了它们对包封率（EE，Y）以及6小时后透过皮肤的红霉素总量（Q6h，Y）的影响。优化后的传递体粒径为256.2 nm，包封率为67.96±0.59%，6小时后的Q6h为665.96±5.87（μg/cm）。透射电镜分析表明，这些囊泡是结构紧密的球形。使用羟丙基甲基纤维素（HPMC）作为凝胶剂，将优化后的传递体制剂进一步转化为基于肉桂油的乳化凝胶系统。制备的EM - TE - 乳化凝胶通过其物理特性、体外和离体研究以及抗菌活性进行表征。该制剂具有有效局部应用的充分特性，并表现出良好的稳定性。此外，EM - TE - 乳化凝胶具有最高的透皮通量（120.19μg/cm·h），并且与EM - TE - 凝胶和安慰剂TE - 乳化凝胶相比，其抗菌活性显著更高（P < 0.05）。红霉素的作用随后因肉桂油而增强，最终对细菌生长显示出显著效果。最后，这些结果表明，基于肉桂油的负载传递体的乳化凝胶是递送红霉素用于治疗局部细菌感染的一种替代方法。
