title: Dissolution enhancement of active pharmaceutical ingredients by therapeutic deep eutectic systems.
abstract: A therapeutic deep eutectic system (THEDES) is here defined as a deep eutectic solvent (DES) having an active pharmaceutical ingredient (API) as one of the components. In this work, THEDESs are proposed as enhanced transporters and delivery vehicles for bioactive molecules. THEDESs based on choline chloride (ChCl) or menthol conjugated with three different APIs, namely acetylsalicylic acid (AA), benzoic acid (BA) and phenylacetic acid (PA), were synthesized and characterized for thermal behaviour, structural features, dissolution rate and antibacterial activity. Differential scanning calorimetry and polarized optical microscopy showed that ChCl:PA (1:1), ChCl:AA (1:1), menthol:AA (3:1), menthol:BA (3:1), menthol:PA (2:1) and menthol:PA (3:1) were liquid at room temperature. Dissolution studies in PBS led to increased dissolution rates for the APIs when in the form of THEDES, compared to the API alone. The increase in dissolution rate was particularly noticeable for menthol-based THEDES. Antibacterial activity was assessed using both Gram-positive and Gram-negative model organisms. The results show that all the THEDESs retain the antibacterial activity of the API. Overall, our results highlight the great potential of THEDES as dissolution enhancers in the development of novel and more effective drug delivery systems.
authors.affiliation: 3B's Research Group - Biomaterials, Biodegradable and Biomimetic, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark, 4805-017 Barco, Guimarães, Portugal; ICVS/3B's PT Government Associated Laboratory, Braga/Guimarães, Portugal.
authors.forename: Ivo M
authors.initials: IM
authors.lastname: Aroso
authors.affiliation: 3B's Research Group - Biomaterials, Biodegradable and Biomimetic, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark, 4805-017 Barco, Guimarães, Portugal; ICVS/3B's PT Government Associated Laboratory, Braga/Guimarães, Portugal.
authors.forename: João C
authors.initials: JC
authors.lastname: Silva
authors.affiliation: LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
authors.forename: Francisca
authors.initials: F
authors.lastname: Mano
authors.affiliation: UCIBio-REQUIMTE, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal; Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
authors.forename: Ana S D
authors.initials: AS
authors.lastname: Ferreira
authors.affiliation: LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
authors.forename: Madalena
authors.initials: M
authors.lastname: Dionísio
authors.affiliation: UCIBio-REQUIMTE, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Sá-Nogueira
authors.affiliation: LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: Barreiros
authors.affiliation: 3B's Research Group - Biomaterials, Biodegradable and Biomimetic, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark, 4805-017 Barco, Guimarães, Portugal; ICVS/3B's PT Government Associated Laboratory, Braga/Guimarães, Portugal.
authors.forename: Rui L
authors.initials: RL
authors.lastname: Reis
authors.affiliation: LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Paiva
authors.affiliation: 3B's Research Group - Biomaterials, Biodegradable and Biomimetic, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark, 4805-017 Barco, Guimarães, Portugal; ICVS/3B's PT Government Associated Laboratory, Braga/Guimarães, Portugal. Electronic address: aduarte@dep.uminho.pt.
authors.forename: Ana Rita C
authors.initials: AR
authors.lastname: Duarte
mesh_terms: D002152:Calorimetry, Differential Scanning; D004339:Drug Compounding; D016503:Drug Delivery Systems; D009682:Magnetic Resonance Spectroscopy; D014677:Pharmaceutical Vehicles; D012995:Solubility; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D014677:Pharmaceutical Vehicles; D012997:Solvents
keywords: Drug solubility; Green technologies; Pharmaceutical and biomedical applications; Therapeutic deep eutectic systems