Publications and Research
Document Type
Article
Publication Date
9-2-2026
Abstract
Transdermal delivery of high-molecular-weight proteins is challenging because of their large molecular size and hydrophilicity, and the barrier properties of the stratum corneum. We report a hydrated ionic liquid-in-oil (HIL/O) microemulsion for transdermal delivery of high-molecular-weight proteins. A biocompatible ionic liquid (IL) composed of cholinium cation and propionate anion, optimized at 45 wt% hydration, was developed as a protein-compatible solubilization medium that dissolved ovalbumin (molecular mass ∼ 45 kDa) and bovine serum albumin (molecular mass ∼ 66 kDa), whereas lower hydration levels were insufficient for effective protein dissolution. Following solubilization, circular dichroism spectroscopy showed recovery of the native-like secondary structures following removal of hydrated [Cho][Pro] IL by dialysis. The protein-loaded hydrated IL phase was dispersed into an HIL/O microemulsion comprising choline linoleate, sorbitan monolaurate (Span 20), polyethylene glycol 400 and isopropyl myristate. Dynamic light scattering and transmission electron microscopy showed that colloidally stable nanosized droplets with diameters of 30–50 nm formed. In vitro Franz diffusion studies across mouse and Yucatan micropig skin demonstrated a 22- to 62-fold increase in cumulative permeation for both proteins compared with the phosphate-buffered saline controls. Increased transdermal skin retention was confirmed by confocal microscopy, confirming deeper skin distribution of the protein. Fourier-transform infrared spectroscopy showed disruption and fluidization of stratum corneum lipid organization, suggesting an IL-mediated permeation mechanism. Histopathological and cytotoxicity studies confirmed favorable skin compatibility and cell viability above 85%. These findings demonstrate that the hydration-controlled IL platform enables stabilization and increased transdermal delivery of high-molecular-weight proteins, offering a promising non-invasive approach for macromolecular therapeutics and vaccines.
Comments
This article was originally published in Journal of Molecular Liquids, available at https://doi.org/10.1016/j.molliq.2026.129902.
This work is distributed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).