Faculty of Pharmacy, Department of Pharmaceutics, Bahauddin Zakariya University, Multan, Pakistan.
Institute of Pure and Applied Biology, Bahauddin Zakariya University, Multan, Pakistan.
PLoS One. 2022 Apr 7;17(4):e0258355. doi: 10.1371/journal.pone.0258355. eCollection 2022.
Naturally occurring curcumin can be used for the treatment of corneal bacterial infections with its limitation of poor solubility. Aim of the present study was to enhance solubility and permeation of curcumin for the treatment of corneal bacterial infections. For increasing solubility, curcumin and polyethylene glycol (PEG 6000) complex (1:3) was prepared by fusion melting method. Phase solubility studies were used for the calculation of Gibbs free energy of curcumin. Central composite rotatable design (CCRD) was applied for optimization of Curcumin (CUR), PEGylated Curcumin (PEG-CUR), penetration enhancer cremophore (CR). Optimized ointments were further evaluated by mucous permeation, membrane permeability and cell toxicity studies by Transwell cell, ussing chamber and Caco-2 cells respectively. Antibacterial test was also performed by agar well diffusion method. Solubility of PEG-CUR was increased up to 93±3.2% as compared to pure curcumin and content uniformity was in the range of 95-110%. Curcumin permeation from PEG-CUR ointment was increased up to 12 folds. No toxicity of Caco-2 cells for PEG-CUR even after 24h was observed. Activity index of pure CUR, PEG-CUR ointment with or without CR against S. aureus and P. aeruginosa was 97±2.3, 96±1.6, 95±2.5% respectively. Ointment with solubility enhanced PEG-CUR and cremophore can be used as a promising tool for the treatment of corneal bacterial infections.
天然姜黄素可用于治疗角膜细菌性感染，但存在溶解度差的局限性。本研究旨在提高姜黄素的溶解度和渗透性，以治疗角膜细菌性感染。为了提高溶解度，采用熔融法制备了姜黄素与聚乙二醇（PEG 6000）的复合物（1:3）。相溶解度研究用于计算姜黄素的吉布斯自由能。采用中心复合旋转设计（CCRD）优化姜黄素（CUR）、聚乙二醇化姜黄素（PEG-CUR）、渗透增强型表面活性剂 Cremophor（CR）。通过 Transwell 细胞、使用室和 Caco-2 细胞分别进行粘膜渗透、膜通透性和细胞毒性研究，进一步评估优化的软膏。通过琼脂孔扩散法进行抗菌试验。与纯姜黄素相比，PEG-CUR 的溶解度提高了 93±3.2%，含量均匀度在 95-110%范围内。PEG-CUR 软膏中姜黄素的渗透增加了 12 倍。即使在 24 小时后，Caco-2 细胞对 PEG-CUR 也没有毒性。纯 CUR、含或不含 CR 的 PEG-CUR 软膏对金黄色葡萄球菌和铜绿假单胞菌的活性指数分别为 97±2.3%、96±1.6%和 95±2.5%。具有增强溶解度的 PEG-CUR 和表面活性剂的软膏可作为治疗角膜细菌性感染的有前途的工具。
