Development of phenyllactic acid ionic liquids and evaluation of cytotoxicity to human cervical epithelial cells

Abstract

Phenyllactic acid (PLA), is a naturally produced, broad-spectrum antimicrobial compound with activity against bacteria and fungi. PLA can be produced by a variety of lactic acid bacteria, including vaginal Lactobacillus species, which are healthy constituents of the vaginal microbiome with a protective role against invading pathogenic bacteria and/or fungi. Additionally, PLA has been shown to exhibit anti-inflammatory and immunomodulatory properties, overall indicating its therapeutic potential as an intravaginally delivered compound for modulation of the vaginal microbiome. However, PLA has low kinetic solubility in water. Hence, strategies to improve the solubility of PLA are necessary to facilitate its intravaginal delivery. Using biocompatible cations, choline and carnitine, we successfully transformed both d- and l-enantiomers of crystalline PLA into amorphous low-melting ionic liquids (ILs) with high water solubility. We further evaluated the in vitro cytotoxicity of PLA ILs to human cervical epithelial cells. Microscopic visualisation of cellular morphology using crystal violet staining and MTT cell proliferation assay revealed that PLA ILs result in minimal morphological changes and low cytotoxicity to human cervical epithelial cells. Overall, we successfully demonstrated that transforming PLA into ILs efficiently enhances its solubility in water and these formulations are not toxic to human epithelial cells. This investigation lays the groundwork for future testing of PLA ILs for their antimicrobial properties and metabolic activity within the cervicovaginal microenvironment.