Drug Delivery Applications of Hydrophobic Deep Eutectic Solvent-in-Water Nanoemulsions

Syed, Usman T.; Calzada, Javier; Mendoza, Gracia; Arruebo, Manuel; Piacentini, Emma; Giorno, Lidietta; Crespo, João G.; Brazinha, Carla; Sebastian, Victor

http://hdl.handle.net/10362/185003

Utilize este identificador para referenciar este registo.

Nome:	Descrição:	Tamanho:	Formato:
Syed_U._T._et_al._2025_..pdf		5.7 MB	Adobe PDF	Ver/Abrir

Contacte-nos

Autores

Resumo(s)

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 “n” 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.

Descrição

Funding Information: The authors would like to acknowledge the Executive Agency for Education, Audiovisual, and Culture (EACEA) of the European Commission for the scholarship grant of Erasmus Mundus Doctorate in Membrane Engineering (EUDIME) program to Syed Usman Taqui. Prof. Reyes Mallada and Dr. Ruth Lahoz from the Nanoscience Institute of Aragon (INA), University of Zaragoza, are acknowledged for their unconditional support in fabrication and characterization of metallic membranes. This work was also supported by the Associate Laboratory for Green Chemistry-LAQV which is financed by national funds from FCT/MCTES (UIDB/50006/2020). V.S. acknowledges the financial support by the Spanish Ministry of Science and Innovation (grant no. PID2021-127847OB-I00). We also acknowledge the financial support of the NextGenerationEU/PRTR thanks to the project: PDC2022-133866-I00. CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program. G.M. gratefully acknowledges the support from the Miguel Servet Program (MS19/00092; Instituto de Salud Carlos III). INMA researchers thank the Severo Ochoa Grant CEX2023-001286-S funded by MICIU/ AEI/10.13039/501100011033. Authors thank the “Advanced Microscopy Laboratory” ELECMI and NANBIOSIS ICTSs, for access to their instruments. Part of the work was supported within the Bio4Mem project (CNR-DCM.AD006.234). Publisher Copyright: © 2024 The Authors.