Presentation Information
[1AFOB-04]Non-Invasive mRNA Vaccination via Ionic Liquid Crystals for Robust Antitumor Immunity
○Masahiro Goto1, Tomohiro Higashi1 (1. Kyushu University (Japan))
Keywords:
mRNA Vaccination,Transdermal delivery,DDS,Ionic liquids,Liquid liquid crystals
[Purpose]
mRNA vaccines have emerged as a promising therapeutic modality due to their ability to elicit strong immune responses, their low risk of genomic integration, and their potential for the rapid production of diverse vaccine candidates using a unified manufacturing platform. However, current mRNA vaccines primarily rely on injection-based administration, which is invasive and requires trained healthcare professionals.
[Method]
To address these limitations, transdermal administration has been proposed as a non-invasive alternative. However, the stratum corneum (SC) serves as a formidable barrier to the penetration of biopharmaceuticals, necessitating innovative strategies for effective transdermal vaccination. In this study, we developed a novel ionic liquid crystal (ILC) system derived from lyotropic liquid crystals (LLCs) using an amphiphilic ionic liquid (IL). The ILC formulation was prepared by mixing the IL with ultrapure water and exhibited viscoelastic properties suitable for transdermal delivery. In this study, we used mRNA encoding OVA257-264 (SIINFEKL) as a model antigen, but this approach is expected to be applicable to other mRNAs encoding different proteins.
[Results]
Various ILCs were prepared by altering the weight ratio of ultrapure water to IL, and their physicochemical properties were evaluated. All tested ILCs exhibited suitable rheological properties and RNase resistance, making them promising candidates for transdermal formulations. Notably, among the three types of ILCs examined, ILC30 demonstrated the highest skin permeability. This enhanced permeability was attributed to the interaction between ILC30 and the intercellular lipids in the SC. In vitro skin permeation studies demonstrated that the ILC formulation significantly enhanced mRNA permeability compared with an aqueous mRNA solution. Furthermore, in vivo evaluation using a mouse tumor model showed that transdermal mRNA delivery via the ILC significantly suppressed tumor growth and promoted the infiltration of CD8plus T cells into tumor tissue, indicating a potent antitumor immune response.
[Conclusion]
The ILC-based transdermal delivery system offers significant advantages, including enhanced skin permeability, mRNA stability, and non-invasiveness. However, its formulation complexity may present challenges compared to more established methods like microneedles and iontophoresis. Despite these challenges, the ILC system holds great promise for the non-invasive delivery of mRNA vaccines and other biomacromolecules, paving the way for future advancements in transdermal drug delivery.
mRNA vaccines have emerged as a promising therapeutic modality due to their ability to elicit strong immune responses, their low risk of genomic integration, and their potential for the rapid production of diverse vaccine candidates using a unified manufacturing platform. However, current mRNA vaccines primarily rely on injection-based administration, which is invasive and requires trained healthcare professionals.
[Method]
To address these limitations, transdermal administration has been proposed as a non-invasive alternative. However, the stratum corneum (SC) serves as a formidable barrier to the penetration of biopharmaceuticals, necessitating innovative strategies for effective transdermal vaccination. In this study, we developed a novel ionic liquid crystal (ILC) system derived from lyotropic liquid crystals (LLCs) using an amphiphilic ionic liquid (IL). The ILC formulation was prepared by mixing the IL with ultrapure water and exhibited viscoelastic properties suitable for transdermal delivery. In this study, we used mRNA encoding OVA257-264 (SIINFEKL) as a model antigen, but this approach is expected to be applicable to other mRNAs encoding different proteins.
[Results]
Various ILCs were prepared by altering the weight ratio of ultrapure water to IL, and their physicochemical properties were evaluated. All tested ILCs exhibited suitable rheological properties and RNase resistance, making them promising candidates for transdermal formulations. Notably, among the three types of ILCs examined, ILC30 demonstrated the highest skin permeability. This enhanced permeability was attributed to the interaction between ILC30 and the intercellular lipids in the SC. In vitro skin permeation studies demonstrated that the ILC formulation significantly enhanced mRNA permeability compared with an aqueous mRNA solution. Furthermore, in vivo evaluation using a mouse tumor model showed that transdermal mRNA delivery via the ILC significantly suppressed tumor growth and promoted the infiltration of CD8plus T cells into tumor tissue, indicating a potent antitumor immune response.
[Conclusion]
The ILC-based transdermal delivery system offers significant advantages, including enhanced skin permeability, mRNA stability, and non-invasiveness. However, its formulation complexity may present challenges compared to more established methods like microneedles and iontophoresis. Despite these challenges, the ILC system holds great promise for the non-invasive delivery of mRNA vaccines and other biomacromolecules, paving the way for future advancements in transdermal drug delivery.
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