Pharmaceutical Technology Department, National Research Centre, Dokki, Cairo 12622, Egypt.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ahram Canadian University, 6(th) of October City, Cairo, Egypt.
Int J Pharm. 2023 Nov 5;646:123487. doi: 10.1016/j.ijpharm.2023.123487. Epub 2023 Oct 5.
This study aims to develop a pharmaceutical formulation that combines the potent antibacterial effect of lincomycin and lauric acid against Cutibacterium acnes (C. acnes), a bacterium implicated in acne. The selection of lauric acid was based on an in silico study, which suggested that its interaction with specific protein targets of C. acnes may contribute to its synergistic antibacterial and anti-inflammatory effects. To achieve our aim, glycerosomes were fabricated with the incorporation of lauric acid as a main constituent of glycerosomes vesicular membrane along with cholesterol and phospholipon 90H, while lincomycin was entrapped within the aqueous cavities. Glycerol is expected to enhance the cutaneous absorption of the active moieties via hydrating the skin. Optimization of lincomycin-loaded glycerosomes (LM-GSs) was conducted using a mixed factorial experimental design. The optimized formulation; LM-GS4 composed of equal ratios of cholesterol:phospholipon90H:Lauric acid, demonstrated a size of 490 ± 17.5 nm, entrapment efficiency-values of 90 ± 1.4 % for lincomycin, and97 ± 0.2 % for lauric acid, and a surface charge of -30.2 ± 0.5mV. To facilitate its application on the skin, the optimized formulation was incorporated into a carbopol hydrogel. The formed hydrogel exhibited a pH value of 5.95 ± 0.03 characteristic of pH-balanced skincare and a shear-thinning non-Newtonian pseudoplastic flow. Skin deposition of lincomycin was assessed using an in-house developed and validated LC-MS/MS method employing gradient elution and electrospray ionization detection. Results revealed that LM-GS4 hydrogel exhibited a two-fold increase in skin deposition of lincomycin compared to lincomycin hydrogel, indicating improved skin penetration and sustained release. The synergistic healing effect of LM-GS4 was evidenced by a reduction in inflammation, bacterial load, and improved histopathological changes in an acne mouse model. In conclusion, the proposed formulation demonstrated promising potential as a topical treatment for acne. It effectively enhanced the cutaneous absorption of lincomycin, exhibited favorable physical properties, and synergistic antibacterial and healing effects. This study provides valuable insights for the development of an effective therapeutic approach for acne management.
本研究旨在开发一种药物制剂，将林可霉素和月桂酸的强大抗菌作用结合起来，针对痤疮丙酸杆菌（C. acnes），这种细菌与痤疮有关。选择月桂酸是基于一项计算机研究，该研究表明，它与 C. acnes 特定的蛋白质靶标相互作用可能有助于其协同的抗菌和抗炎作用。为了实现我们的目标，甘油体被制造出来，其中包含月桂酸作为甘油体囊泡膜的主要成分，同时还包含胆固醇和磷脂 90H，而林可霉素则被包裹在水腔中。甘油预计通过滋润皮肤来增强活性物质的皮肤吸收。使用混合因子实验设计对载有林可霉素的甘油体（LM-GS）进行了优化。优化的配方；由胆固醇：磷脂 90H：月桂酸组成的比例相等的 LM-GS4，其粒径为 490 ± 17.5nm，林可霉素的包封效率值为 90 ± 1.4%，月桂酸的包封效率值为 97 ± 0.2%，表面电荷为-30.2 ± 0.5mV。为了方便其在皮肤上的应用，将优化的配方掺入卡波姆水凝胶中。形成的水凝胶具有 5.95 ± 0.03 的 pH 值，具有平衡皮肤的 pH 值，并且具有剪切稀变的非牛顿假塑性流。使用内部开发和验证的 LC-MS/MS 方法，采用梯度洗脱和电喷雾电离检测，评估了林可霉素在皮肤中的沉积。结果表明，与林可霉素水凝胶相比，LM-GS4 水凝胶使林可霉素在皮肤中的沉积增加了两倍，表明其皮肤渗透和持续释放得到了改善。LM-GS4 的协同愈合作用通过减少炎症、细菌负荷和改善痤疮小鼠模型的组织病理学变化得到证明。总之，所提出的配方具有作为痤疮局部治疗的潜在前景。它有效地增强了林可霉素的皮肤吸收，表现出良好的物理性质，并具有协同的抗菌和愈合作用。本研究为开发有效的痤疮管理治疗方法提供了有价值的见解。
