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. 2024 Jun 24;29(13):2995.
doi: 10.3390/molecules29132995.

Ionic Liquid-Based Immunization Patch for the Transdermal Delivery of Antigens

Rashedul Islam  1 , Fahmida Habib Nabila  1 , Rie Wakabayashi  1   2   3 , Yoshirou Kawaguchi  1 , Noriho Kamiya  1   2   3 , Muhammad Moniruzzaman  4 , Masahiro Goto  1   2   3
Affiliations

Ionic Liquid-Based Immunization Patch for the Transdermal Delivery of Antigens

Rashedul Islam et al. Molecules. .

Abstract

Herein, we report a transdermal patch prepared using an ionic liquid-based solid in oil (IL-S/O) nanodispersion and a pressure-sensitive adhesive (PSA) to deliver the macromolecular antigenic protein, ovalbumin (OVA). The IL-S/O nanodispersion and a PSA were first mixed at an equal weight ratio, then coated onto a release liner, and covered with a support film. To evaluate the effect of the PSA, three types of PSAs, DURO-TAK 87-4098, DURO-TAK 87-4287, and DURO-TAK 87-235A, were used to obtain the corresponding IL-S/O patches SP-4098, SP-4287, and SP-235A, respectively. The prepared IL-S/O patches were characterized for surface morphology, viscoelasticity, and moisture content. In vitro skin penetration and in vivo immunization studies of the IL-S/O patches were performed using Yucatan micropig skin and the C57BL/6NJc1 mice model, respectively. The SP-4098 and SP-4287 delivered 5.49-fold and 5.47-fold higher amounts of drug compared with the aqueous formulation. Although both patches delivered a similar amount of drug, SP-4287 was not detached fully from the release liner after 30 days, indicating low stability. Mice immunized with the OVA-containing SP-4098 produced a 10-fold increase in anti-OVA IgG compared with those treated with an aqueous formulation. These findings suggested that the IL-S/O patch may be a good platform for the transdermal delivery of antigen molecules.

Keywords: IL-S/O patch; immunization; ionic liquid; pressure-sensitive adhesive; transdermal drug delivery.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Structure of Ionic Liquid (IL) and (B) general outline of the IL-S/O patch preparation.
Figure 2
Figure 2
Scanning electronic microscopy (SEM) images of SP-4098 and SP-4287. The magnification is 1000× and the applied voltage was 15.0 kV. The scale bar is 10 µm.
Figure 3
Figure 3
Percentage of moisture content and moisture uptake by SP-4098 and SP-4287.
Figure 4
Figure 4
Viscoelastic properties of the IL-S/O patches; 8.5% HEC gel was used as a control gel.
Figure 5
Figure 5
Stability of the IL-S/O patches; (A) illustrates the peeling characteristics of the IL-S/O patches after 30 days and (B) shows the amount of OVA present in the patches initially and after 30 days.
Figure 6
Figure 6
Penetration of FITC-OVA in YMP skin after 24 h of administration (A) and amounts of OVA delivered transdermally and topically after 24 h (B). All data presented are the means of three samples ± SD. *** p < 0.001.
Figure 7
Figure 7
FTIR spectroscopic investigation of the SC layer after treatment with the IL-S/O patches. Spectra and peak position changes for (A) symmetric CH2 stretches and (B) asymmetric CH2 stretches. All data are the means of three samples ± SD. *** p < 0.001.
Figure 8
Figure 8
Results of the in vitro skin irritation study of the IL-S/O patches using the EPI-MODEL 24. Data are presented as the means of three samples ± SD. ns: non-significant, *** p < 0.001.
Figure 9
Figure 9
In vivo immunization study design (A) and anti-OVA IgG titer after 28 and 56 days of immunization (B). Data are presented as the means of five samples ± SD. *** p < 0.001.
See this image and copyright information in PMC

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