# Ionic Liquid-Enabled Drug Delivery Systems: Benefits, Limitations, and Future Perspectives

**Authors:** Daeyeong Lee, Sooa Lim

PMC · DOI: 10.3390/pharmaceutics18020224 · 2026-02-10

## TL;DR

This paper reviews how ionic liquids can be used in drug delivery systems to improve drug properties and delivery performance, while addressing challenges like toxicity and regulatory issues.

## Contribution

The paper provides a comprehensive review of ionic liquid-based drug delivery strategies, emphasizing formulation design and mechanistic insights.

## Key findings

- Ionic liquids enhance drug solubility, stability, and permeability through complex formation and membrane interactions.
- Formulation design principles are critical for optimizing delivery performance and safety of ionic liquid-based systems.
- Toxicity, scalability, and regulatory challenges remain significant barriers to clinical translation of ionic liquid-enabled drug delivery systems.

## Abstract

ILs have emerged as versatile formulation components in DDS due to their tunable physicochemical properties and ability to modulate biomolecular and interfacial interactions. This review examines IL-enabled DDS strategies across major delivery platforms, including nanocarrier-based systems, microtechnology-assisted devices, and biomacromolecule formulations, with emphasis on formulation design principles rather than administration route. We discuss how ILs enhance API solubility, stability, permeability, and formulation flexibility through API–IL complex formation and controlled membrane interactions and relate mechanistic insights into IL–membrane interactions to both delivery performance and safety via structure–activity relationships. Current limitations, including toxicity concerns, lack of standardized evaluation criteria, scalability challenges, and regulatory ambiguity, are critically assessed. Overall, this review positions ILs as formulation-enabling materials rather than standalone therapeutics and underscores the importance of rational design, standardized assessment, and early regulatory alignment for advancing IL-enabled DDS toward clinical translation.

## Full-text entities

- **Genes:** GH1 (growth hormone 1) [NCBI Gene 2688] {aka GH, GH-N, GHB5, GHN, IGHD1A, IGHD1B}, ABCB1 (ATP binding cassette subfamily B member 1) [NCBI Gene 5243] {aka ABC20, CD243, CLCS, ENPAT, GP170, MDR1}, LYZ (lysozyme) [NCBI Gene 4069] {aka AMYLD5, LYZF1, LZM}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}
- **Diseases:** brain cancer (MESH:D001932), DDS (MESH:D000014), Toxicity (MESH:D064420), infection (MESH:D007239), autoimmune diseases (MESH:D001327), pain (MESH:D010146), injury to (MESH:D014947), inflammatory (MESH:D007249), cancer (MESH:D009369)
- **Chemicals:** HSA (MESH:D006585), lipid (MESH:D008055), citric acid (MESH:D019343), Emim][Ac (MESH:C518739), ampicillin (MESH:D000667), ROS (MESH:D017382), hydrogen (MESH:D006859), PLGA (MESH:D000077182), acetate (MESH:D000085), silica (MESH:D012822), DOX (MESH:D004317), sulfoxides (MESH:D013454), BF4- (-), SCN (MESH:C031760), amino acid (MESH:D000596), pravadoline (MESH:C062767), BMIM][Br (MESH:C502841), MTX (MESH:D008727), water (MESH:D014867), lapatinib (MESH:D000077341), ethanol (MESH:D000431), acyclovir (MESH:D000212), methicillin (MESH:D008712), trans fatty acids (MESH:D044242), sorafenib (MESH:D000077157), ethylammonium nitrate (MESH:C421484), alginate (MESH:D000464), salicylic acid (MESH:D020156), favipiravir (MESH:C462182), chitosan (MESH:D048271), DCA (MESH:D003840), metal (MESH:D008670), carbon (MESH:D002244), polymer (MESH:D011108), CIP (MESH:D002939), Choline (MESH:D002794), ammonium (MESH:D064751)
- **Species:** Homo sapiens (human, species) [taxon 9606], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Staphylococcus aureus (species) [taxon 1280], Escherichia coli (E. coli, species) [taxon 562], Bacillus subtilis (species) [taxon 1423], Cutibacterium acnes (species) [taxon 1747]
- **Cell lines:** T98G — Homo sapiens (Human), Glioblastoma, Cancer cell line (CVCL_0556), HEK — Homo sapiens (Human), Transformed cell line (CVCL_0045), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), 3T3-L1 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0123)

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12944413/full.md

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Source: https://tomesphere.com/paper/PMC12944413