Syed Usman T, Calzada Javier, Mendoza Gracia, Arruebo Manuel, Piacentini Emma, Giorno Lidietta, Crespo João G, Brazinha Carla, Sebastian Victor
LAQV/Requimte, Department of Chemistry, NOVA School of Science and Technology, FCT NOVA, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal.
Department of Chemical Engineering and Environmental Technology, Universidad de Zaragoza, Campus Río Ebro-Edificio I+D, 50018 Zaragoza, Spain.
ACS Appl Mater Interfaces. 2025 Jan 15;17(2):4075-4086. doi: 10.1021/acsami.4c13163. Epub 2024 Dec 31.
The emergence of green chemistry and engineering principles to enforce sustainability aspects has ensured the prevalence of green solvents and green processes. Our study addresses this quest by exploring drug delivery applications of hydrophobic deep eutectic solvents (DESs) which are alternative green solvents. Initially, this work showcases the hydrophobic drug solubilization capabilities of a natural hydrophobic DES, menthol, and decanoic acid. To consider biomedical applications wherein polar media are encountered, this work further demonstrates the potential drug delivery application of these systems by encapsulating the anti-inflammatory local anesthetic lidocaine in hydrophobic DES-in-water nanoemulsions. NMR studies confirm the high solubility of the hydrophobic drug in hydrophobic DES comprising menthol and decanoic acid (1:2 molar ratio). Ultrasound emulsification and energy-efficient membrane emulsification techniques were employed to disperse 4% (v/v) DES into a 2% (w/w) Tween 20 surfactant aqueous solution. An isoporous microengineered membrane (nominal pore size ∼ 9 μm) was used to produce lidocaine-loaded DES-based nanoemulsions. Such membrane-assisted nanoemulsification was possible because the hydrophobic DES exhibits relatively low interfacial tension with the continuous phase and acts as a cosurfactant. Moreover, increased concentrations of lidocaine within the DES resulted in a further decrease in the interfacial tension and a lower melting point. Among the kinetic models analyzed to evaluate the release of lidocaine encapsulated in hydrophobic DES-in-water nanoemulsions, the Korsmeyer-Peppas kinetic model provided the best fit. The release constant "" of <0.5 indicates that the drug release mechanism is predominantly governed by diffusion. Additionally, cytotoxicity against various human cell lines demonstrated the nanoemulsion's potential for anti-inflammatory drug delivery applications. Consequently, the nanoemulsion of DES presents a promising solution for the effective loading and delivery of poorly soluble drugs. This innovative approach enhances drug solubility and bioavailability, providing a versatile platform for controlled drug release. By leveraging the advantages of nanoemulsion technology, our study underscores the potential of DES-based formulations to promote drug delivery systems across a variety of therapeutic applications.
绿色化学与工程原理的出现，旨在强化可持续发展方面，确保了绿色溶剂和绿色工艺的广泛应用。我们的研究通过探索疏水性低共熔溶剂（DESs）的药物递送应用来解决这一问题，疏水性低共熔溶剂是一类替代性绿色溶剂。最初，这项工作展示了天然疏水性DES（薄荷醇和癸酸）对疏水性药物的增溶能力。为了考虑在极性介质中遇到的生物医学应用，这项工作进一步通过将抗炎局部麻醉药利多卡因包裹在疏水性水包DES纳米乳剂中，展示了这些体系潜在的药物递送应用。核磁共振研究证实了疏水性药物在由薄荷醇和癸酸（摩尔比1:2）组成的疏水性DES中的高溶解度。采用超声乳化和节能膜乳化技术将4%（v/v）的DES分散到2%（w/w）吐温20表面活性剂水溶液中。使用等孔微工程膜（标称孔径约9μm）来制备载有利多卡因的DES基纳米乳剂。这种膜辅助纳米乳化是可行的，因为疏水性DES与连续相表现出相对较低的界面张力，并充当助表面活性剂。此外，DES中利多卡因浓度的增加导致界面张力进一步降低和熔点降低。在分析用于评估包裹在疏水性水包DES纳米乳剂中利多卡因释放的动力学模型中，Korsmeyer-Peppas动力学模型拟合效果最佳。释放常数“”<0.5表明药物释放机制主要受扩散控制。此外，对各种人类细胞系的细胞毒性证明了纳米乳剂在抗炎药物递送应用中的潜力。因此，DES纳米乳剂为有效负载和递送难溶性药物提供了一个有前景的解决方案。这种创新方法提高了药物溶解度和生物利用度，为药物控释提供了一个通用平台。通过利用纳米乳剂技术的优势，我们的研究强调了基于DES的制剂在促进跨多种治疗应用的药物递送系统方面的潜力。
