title: Characterization and antimicrobial phototoxicity of curcumin dissolved in natural deep eutectic solvents.
abstract: Natural deep eutectic solvents (NADES) are a novel class of eutectics which show a unique potential as solubilizer of water insoluble compounds. The purpose of the current study was to evaluate the potential of NADES as a solvent for the hydrophobic photosensitizer curcumin for use in antimicrobial photodynamic therapy (aPDT). Two of the seventeen NADES initially prepared (i.e., NADES GS and MC3) solubilized >0.05mg/ml curcumin and were further characterized. The hydrolytic stability (i.e., t1/2) of curcumin in NADES was comparable to or up to 2-10 times higher than previously reported results in cyclodextrins and up to >1300 times higher than results reported in buffer at pH8. The photolytic stability increased by a factor 5.6-10 in GS compared to the most photostable cyclodextrin and surfactant preparations reported previously. This NADES seemed to lock curcumin in its colorless diketo conformer, resulting in higher photostability than in ethanol and in the NADES MC3. The curcumin-NADES preparations dissolved rapidly in aqueous media and formed supersaturated solutions of curcumin. Precipitation of curcumin was observed after ≤1h depending on the dilution factor (pH<8). The NADES MC3 containing curcumin photoinactivated Escherichia coli at a lower curcumin concentration (1.25μM) than in any previously investigated preparations of curcumin. The ability of NADES to lock curcumin within one specific molecular conformation and also to potentiate the phototoxic effect of this photosensitizer emphasizes the unique properties of the NADES as a solvent.
authors.affiliation: Department of Pharmacy, School of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, 0316 Oslo, Norway. Electronic address: k.o.wikene@farmasi.uio.no.
authors.forename: Kristine Opsvik
authors.initials: KO
authors.lastname: Wikene
authors.affiliation: Nordic Institute of Dental Materials AS, Sognsveien 70A, 0855 Oslo, Norway. Electronic address: ellen.bruzell@niom.no.
authors.forename: Ellen
authors.initials: E
authors.lastname: Bruzell
authors.affiliation: Department of Pharmacy, School of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, 0316 Oslo, Norway. Electronic address: h.h.tonnesen@farmasi.uio.no.
authors.forename: Hanne Hjorth
authors.initials: HH
authors.lastname: Tønnesen
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D012997:Solvents
chemical_list: D000900:Anti-Bacterial Agents; D017319:Photosensitizing Agents; D012997:Solvents; D003474:Curcumin
keywords: Antimicrobial photodynamic therapy; Choline chloride (PubChem CID: 6209); Curcumin; Curcumin (PubChem CID: 969516); Diketo conformer; Escherichia coli; Glucose (PubChem CID: 107526); Maleic acid (PubChem CID: 444266); Natural deep eutectic solvents; Solubility; Sucrose (PubChem CID: 5988)