Salicylic Acid as Ionic Liquid Formulation May Have Enhanced Potency to Treat Some Chronic Skin Diseases

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 1; p. 216
• Main Authors: Klebeko, Joanna, Ossowicz-Rupniewska, Paula, Świątek, Ewelina, Szachnowska, Joanna, Janus, Ewa, Taneva, Stefka G, Krachmarova, Elena, Guncheva, Maya
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.12.2021; MDPI
• Subjects: Acne; Administration, Cutaneous; Amino acids; Animals; anti-inflammatory activity; Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Arthritis; Bioavailability; Bovine serum albumin; Cations; Cell Line; Chemistry Techniques, Synthetic; Chronic Disease; Conversion; Cytokines; Cytokines - metabolism; Cytotoxicity; Drug Compounding; Drug dosages; Embryo fibroblasts; Esters; fibroblasts; Humans; Hydrogen-Ion Concentration; Inflammation; Ionic liquids; Ionic Liquids - chemistry; Keratinocytes; Lipopolysaccharides; Mice; Nonsteroidal anti-inflammatory drugs; Pharmaceutical industry; Pharmacokinetics; Physicochemical properties; Psoriasis; Salicylates; Salicylic acid; Salicylic Acid - chemical synthesis; Salicylic Acid - chemistry; Salicylic Acid - pharmacology; salicylic acid-based ionic liquids; Serum albumin; Skin diseases; Skin Diseases - drug therapy; Skin Diseases - etiology; Solubility; Solvents; Thermodynamics; fibroblasts; salicylic acid-based ionic liquids; binding; keratinocytes; bovine serum albumin; cytotoxicity; anti-inflammatory activity
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27010216

In recent years, numerous studies have shown that conversion of conventional drugs in ionic liquid (IL) formulation could be a successful strategy to improve their physicochemical properties or suggest a new route of administration. We report the synthesis and detailed characterization of eight salicylic acid-based ILs (SA-ILs) containing cation non-polar or aromatic amino acid esters. Using in vitro assays, we preliminary evaluated the therapeutic potency of the novel SA-ILs. We observed that conversion of the SA into ionic liquids led to a decrease in its cytotoxicity toward NIH/3T3 murine embryo fibroblasts and human HaCaT keratinocytes. It should be mentioned is that all amino acid alkyl ester salicylates [AAOR][SA] inhibit the production of the proinflammatory cytokine IL-6 in LPS-stimulated keratinocytes. Moreover, keratinocytes, pretreated with [PheOMe][SA] and [PheOPr][SA] seem to be protected from LPS-induced inflammation. Finally, the novel compounds exhibit a similar binding affinity to bovine serum albumin (BSA) as the parent SA, suggesting a similar pharmacokinetic profile. These preliminary results indicate that SA-ILs, especially those with [PheOMe], [PheOPr], and [ValOiPr] cation, have the potential to be further investigated as novel topical agents for chronic skin diseases such as psoriasis and acne vulgaris.