New ibuprofen derivatives were made via conjugation with L-valine alkyl esters (ValOR), where R was changed from an ethyl to a hexyl group. The ionic structure was confirmed using NMR and FTIR. Specific rotation, solubility in commonly used solvents, thermal properties including phase transitions temperatures, and thermal stability were also determined. The ionic structure with a protonated amine group on an L-valine ester and melting points below 100 C allowed inclusion of these ibuprofen derivatives into the pharmaceutically active protic ionic liquids. The ibuprofen salt solubility in deionised water and two buffer solutions at pH 5.4 and 7.4 were established and compared with the parent acid solubility. The octanol/water (buffer) partition coefficient, permeation through porcine skin, and accumulation in the skin were also measured. Ibuprofen pairing with L-valine alkyl esters [ValOR][IBU], caused higher solubility and a greater drug molecule absorption through biological membranes. log P was lower for ibuprofen salts than for the acid and it increased with a longer L-valine ester cation alkyl chain. In vitro porcine skin tests showed that ibuprofen salts with a propyl or isopropyl ester in L-valine are particularly relevant for topical application. They provide transport for ibuprofen through the skin at much higher rate than the unmodified acid and a higher permeated ibuprofen concentration, which can improve efficacy. Thus, synthesised ibuprofen derivatives could be used as drug carriers in transdermal systems to provide better drug bioavailability, and they can be also be the source of exogenous L-valine.

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The effect of various alcohols as vehicles on skin permeability was compared for unmodified ibuprofen (IBU) and ion pairs of ibuprofen with l-valine alkyl esters [ValOR][IBU], in which the alkyl chain R was changed from C1 to C8.

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Amino acid ionic liquid-supported Schiff bases, derivatives of salicylaldehyde and various amino acids (l-threonine, l-valine, l-leucine, l-isoleucine and l-histidine) have been investigated by means of various spectroscopic techniques (NMR, UV-Vis, IR, MS) and deuterium isotope effects on 13C-NMR chemical shifts. The results have shown that in all studied amino acid ionic liquid-supported Schiff bases (except the l-histidine derivative) a proton transfer equilibrium exists and the presence of the COO− group stabilizes the proton transferred NH-form.

The potential of bacterial cellulose as a carrier for the transport of ibuprofen (a typical example of non-steroidal anti-inflammatory drugs) through the skin was investigated. Ibuprofen and its amino acid ester salts-loaded BC membranes were prepared through a simple methodology and characterized in terms of structure and morphology. Two salts of amino acid isopropyl esters were used in the research, namely L-valine isopropyl ester ibuprofenate ([ValOiPr][IBU]) and L-leucine isopropyl ester ibuprofenate ([LeuOiPr][IBU]). [LeuOiPr][IBU] is a new compound; therefore, it has been fully characterized and its identity confirmed. For all membranes obtained the surface morphology, tensile mechanical properties, active compound dissolution assays, and permeation and skin accumulation studies of API (active pharmaceutical ingredient) were determined. The obtained membranes were very homogeneous. In vitro diffusion studies with Franz cells were conducted using pig epidermal membranes, and showed that the incorporation of ibuprofen in BC membranes provided lower permeation rates to those obtained with amino acids ester salts of ibuprofen. This release profile together with the ease of application and the simple preparation and assembly of the drug-loaded membranes indicates the enormous potentialities of using BC membranes for transdermal application of ibuprofen in the form of amino acid ester salts.

This is the first study on the interactions of ionic liquids with large metalloproteins, in particular hemocyanins (Hcs). At first, complexes of a Hc from Rapana thomasiana (RtH) with a series of biocompatible choline amino acid salts [Chol][AA] were obtained. Applying UV-vis spectroscopy, Fouriertransformed infrared spectroscopy and differential scanning calorimetry the effect of these organic salts on the structure and thermal stability of RtH was assessed. Then, the cytotoxic effect of RtH- [Chol][AA] on breast cancer cells (MCF-7) and 3T3 fibroblast cells (non cancerous) was evaluated. We found that all [Chol][AA] induced clear time-and concentration-dependent alterations in the RtH conformation. The conformation and the thermal stability of IL-modified RtH depend strongly on the type of the anion of the tested compounds. All [Chol][AA]-modified RtHs exhibited lower thermal stability than the native RtH. At the same time, we established a good correlation between the structure of RtH and its antitumor activity. Namely, RtH-[Chol][AA] complexes exhibited enhanced antiproliferative activity toward the MCF-7 cell line. The observed antiproliferative effect was cell specific and the compounds have no effect or in some cases have stimulatory effect on fibroblasts. Scheme 1 Synthesis path and structures of cholinium-based amino acid ionic liquids [Chol][AA].This journal is