# Development of Biocompatible Fatty Acid-Based Ionic Liquids for the Effective Topical Treatment of Periodontitis

**Authors:** Mayuko Yanagawa, Mayuka Nakajima, Mayumi Ikeda-Imafuku, Tatsuya Fukuta, Kotone Yoshimura, Chunyang Yan, Lorena Caceres Zegarra, Honoka Takikawa, Truong T. Thien, Ruka Koizumi, Koichi Tabeta

PMC · DOI: 10.1021/acsomega.5c09114 · ACS Omega · 2025-12-29

## TL;DR

Researchers developed new biocompatible ionic liquids from fatty acids that effectively treat periodontitis without causing tissue irritation.

## Contribution

The study introduces fatty acid-based ionic liquids with improved antibiofilm efficacy and safety for topical periodontal treatment.

## Key findings

- Fatty acid-based ionic liquids like [Cho][Ole] and [Cho][Lin] show strong antimicrobial and antibiofilm activity at low concentrations.
- Topical application of these ionic liquids in a mouse model significantly reduced subgingival infection.
- The new ionic liquids demonstrated broader safety margins and no tissue irritation after repeated use.

## Abstract

Periodontitis is a widespread chronic inflammatory disease
characterized
by the progressive destruction of tooth-supporting structures, ultimately
causing tooth loss and impaired quality of life. Pathogenic microorganisms
residing in the periodontal pockets are involved in disease progression.
While antibiotics are widely used, the global rise of antimicrobial
resistance underscores the urgent need for alternative treatments.
Ionic liquids (ILs), which are salts composed of cations and anions
that remain liquid at or near room temperature, have emerged as promising
alternative antimicrobial agents. Their highly tunable nature, achieved
by modifying ion combinations, allows for the development of ILs with
potent antimicrobial activity, such as choline and geranate (CAGE).
However, they can be cytotoxic at concentrations near the therapeutic
effective dose, thereby limiting their clinical application. Moreover,
recent microbiology advances highlight the need for agents that can
effectively target polymicrobial biofilms, which exhibit greater resistance
to treatment than their planktonic counterparts. Therefore, this study
aimed to optimize IL properties based on the CAGE framework by modifying
their ionic composition to enhance their antibiofilm efficacy while
improving their biocompatibility. Fatty acids, commonly found in food,
cosmetics, and skincare products, were selected as alternative anion
donors. Fatty acid-based ILs, particularly choline and oleic acid
([Cho]­[Ole]) and choline and linoleic acid ([Cho]­[Lin]), exhibited
strong antimicrobial and antibiofilm efficacy at markedly lower concentrations.
In a mouse model, topical application of these ILs significantly reduced
subgingival infection. Furthermore, these new ILs demonstrated broader
safety margins and caused no tissue irritation even after repeated
applications. Therefore, rational ion pairing with fatty acid anions
may enhance both ILs’ safety and efficacy, making fatty acid-based
ILs promising candidates as next-generation topical agents for periodontal
therapy.

## Linked entities

- **Chemicals:** choline (PubChem CID 305), geranate (PubChem CID 9549327), oleic acid (PubChem CID 445639), linoleic acid (PubChem CID 5280450)
- **Diseases:** periodontitis (MONDO:0005076)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Diseases:** inflammatory disease (MESH:D007249), Periodontitis (MESH:D010518), infection (MESH:D007239), cytotoxic (MESH:D064420), tooth loss (MESH:D016388)
- **Chemicals:** Cho (MESH:C034482), oleic acid (MESH:D019301), salts (MESH:D012492), Fatty Acid (MESH:D005227), choline (MESH:D002794), CAGE (-), linoleic acid (MESH:D019787)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12809864/full.md

## References

40 references — full list in the complete paper: https://tomesphere.com/paper/PMC12809864/full.md

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Source: https://tomesphere.com/paper/PMC12809864