College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, Zhejiang, China; The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang, China.
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, Zhejiang, China.
Int J Pharm. 2024 Dec 25;667(Pt A):124900. doi: 10.1016/j.ijpharm.2024.124900. Epub 2024 Nov 3.
As a natural small molecule drug derived from turmeric, curcumin is known for its good biosafety and a range of beneficial effects, including anti-inflammatory, anti-spasmodic, antioxidant, antibacterial, anti-tumor, and neuroprotective effects. Even though, its insolubility in water and instability severely limit its bioavailability and clinical applications. The present study developed a deep eutectic solvent (DES) in oil microemulsion (DES/O-ME) system loaded with Cur for intranasal administration, aiming to enhance both the solubility and permeability of Cur to significantly increase its bioavailability. The project first constructed and screened the optimal choline chloride-based DES. Subsequently, the DES/O-ME system was prepared and optimized to achieve uniform particle size and stability using a pseudo-ternary phase diagram and electrical conductivity measurements. The resulting DES/O-ME system was thoroughly evaluated for its solubilization efficacy, permeability, mucosal cytotoxicity, and stability. Additionally, the therapeutic efficacy of the Cur-DES/O-ME was assessed in vivo using a murine model of allergic asthma. This comprehensive evaluation highlights the potential of the DES/O-ME system as a promising intranasal drug delivery platform to overcome the limitations of curcumin's bioavailability and clinical application.
姜黄素是一种天然的小分子药物，来源于姜黄，具有良好的生物安全性和一系列有益的作用，包括抗炎、抗痉挛、抗氧化、抗菌、抗肿瘤和神经保护作用。然而，其在水中的不溶性和不稳定性严重限制了其生物利用度和临床应用。本研究开发了一种用于鼻腔给药的油包二乙基乙酰胺（DES/O-ME）系统负载姜黄素的深共晶溶剂（DES），旨在提高姜黄素的溶解度和通透性，显著提高其生物利用度。该项目首先构建并筛选了最佳的胆碱氯化物基深共晶溶剂。随后，通过伪三元相图和电导率测量来制备和优化 DES/O-ME 系统，以实现均匀的粒径和稳定性。对所得的 DES/O-ME 系统进行了全面评估，包括溶解度、渗透性、黏膜细胞毒性和稳定性。此外，还通过过敏性哮喘小鼠模型评估了姜黄素-DES/O-ME 的治疗效果。这项综合评价突出了 DES/O-ME 系统作为一种有前途的鼻腔给药药物递送平台的潜力，可克服姜黄素生物利用度和临床应用的局限性。
