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

Joanna Klebeko,Ewa Janus,Paula Ossowicz-Rupniewska,Maya Guncheva,Stefka G Taneva,Joanna Szachnowska,Ewelina Świątek,Elena Krachmarova

doi:10.3390/molecules27010216

Abstract

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.

Highlights

The development of innovative drug formulations has been the focus of pharmaceutical research and industry for the last few decades
The different polymorphs of one and the same molecule may have different physicochemical properties, including water solubility, bioavailability, tissue distribution, and therapeutic efficacy [7]. Numerous strategies such as pH adjustment, conversion of the drug into salt form, co-crystallization, use of excipients, particle size reduction, lipid-based formulation, and others have been applied to resolve the problems with low water solubility and stability of drugs [8,9]
We evaluated the cytotoxicity and anti-inflammatory activities of the Salicylic acid (SA)-ionic liquid (IL) on NIH/3T3 murine embryo fibroblasts and human HaCaT keratinocytes

Summary

Introduction

The development of innovative drug formulations has been the focus of pharmaceutical research and industry for the last few decades. The development of novel formulations of oral drugs with enhanced water solubility or proposing alternative routes of administration can be a successful approach to address this problem [4,6] Another major problem of the pharmaceutical industry is the ability of solid drugs to crystallize into different polymorphic forms. The different polymorphs of one and the same molecule may have different physicochemical properties, including water solubility, bioavailability, tissue distribution, and therapeutic efficacy [7] Numerous strategies such as pH adjustment, conversion of the drug into salt form, co-crystallization, use of excipients, particle size reduction, lipid-based formulation, and others have been applied to resolve the problems with low water solubility and stability of drugs [8,9]

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Conclusion