The different faces of nature-inspired ionic liquids and deep eutectic solvents: a promising bioavailability-enhancing development option for pharmaceuticals.

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The Different Faces of Ibuprofen-Based Ionic Liquids and Eutectic Systems: Promising Innovative Ionic-Liquid-Based Formulations of an Over-the-Counter Anti-Inflammatory Drug

Publication . Bastos, Joana Campainhas; Araújo, João; Estévez, Ana

The global goal of the current thesis is to demonstrate the feasibility of the ionic liquids (ILs) platform to boost “old” drugs efficiency. With this ground, cholinium- and imidazolium- based ILs were used to formulate pharmaceutically active ILs (API-ILs) and eutectic systems with ibuprofen (Ibu) as parent active pharmaceutical ingredient (API). The aqueous solubility, water and simulated biological fluids, of the IBU-based ILs and eutectics relatively to Ibu neutral and salt form (sodium ibuprofen) were assessed. Jointly, insights into task-specific fluorinated ILs that reduce the impact of the addition of water upon the IL’s H-bond acceptance ability, a key factor to obtain functionalized materials to be used in the dissolution of drugs or biomolecules, were attained. The cytotoxic profiles were characterized for both IBU-based ILs and eutectics, as well as for the parent API (Ibu), using two human cells lines, colon carcinoma cells (Caco-2) and hepatocellular carcinoma cells (HepG-2). The biocompatibility of all Ibu formulations was also evaluated through a hemolytic activity assay. Moreover, the anti-inflammatory properties of all Ibu formulations, ILs, eutectics, and parent API, were assessed through the inhibition of bovine serum albumin (BSA) denaturation and inhibition of cyclooxygenases (COX-1 and COX-2). The assessment of ionicity, through measurements of density, viscosity, and ionic conductivity, was carried out to evaluate the formation of ion-pairs or clusters that enhance membrane permeation. In the end, an in vitro skin permeation assay was attained through Skin Parallel Artificial Membrane Permeability Assays (Skin-PAMPA) to evaluate the Ibu-based ILs and eutectics skin permeability. The evaluation of the permeation potential allows to guide the design of transdermal drug delivery systems. The results of this thesis comprise a proof of concept for the feasibility of task-specific ILs and IL-based eutectics, namely API-ILs and API-based eutectics, in the development of novel drug delivery systems, and more broadly for biological, biochemical, and pharmaceutical applications.

2023Tese de doutoramento

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Entidade financiadora

Fundação para a Ciência e a Tecnologia

Programa de financiamento

OE

Número da atribuição

COVID/BD/151824/2021