Presentation Information
[P04-479]Ionic Liquid-Based Microemulsions Enable Systemic Delivery of GLP-1 Receptor Agonists via Transdermal Administration
○Yamin Li1, Rie WAKABASHI1, Yoshirou KAWAGUCHI1, Noriho KAMIYA1, Masahiro GOTO1 (1. Kyushu University (Japan))
Keywords:
GLP-1 RA,Transdermal delivery,Ionic Liquid-based Microemulsions
[Purpose]
Diabetes mellitus is a chronic condition characterized by persistently high blood glucose levels. Obesity, a major risk factor for diabetes, continues to rise worldwide. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for treating type 2 diabetes mellitus and obesity by mimicking the effects of the endogenous GLP-1 hormone, which regulates glucose-dependent insulin secretion. However, GLP-1 RAs are primarily administered via injection, which places a significant burden on patients. To improve patient quality of life, we focused on transdermal drug delivery, which offers a non-invasive alternative.
[Method]
Ionic liquids (ILs), defined as organic salts with melting points below 100 °C, have attracted increasing attention as drug delivery enhancers. Choline-based ILs exhibit favorable biocompatibility, structural tunability, and the ability to enhance peptide solubility and skin permeability. In this study, we developed an IL-based microemulsion system as a novel strategy to overcome the skin barrier and reduce the limitations associated with conventional GLP-1 RA administration.
[Results]
Based on the optimized formulation, nanoparticles with an average diameter of approximately 20 nm were successfully prepared and exhibited good stability at room temperature. In vitro Franz diffusion cell experiments demonstrated that the developed system significantly enhanced the transdermal permeation of GLP-1 RAs. Enhanced penetration into deeper skin layers was further confirmed by CLSM imaging. Furthermore, in vivo studies revealed a sustained and stable reduction in blood glucose levels, highlighting the potential of this system as a non-invasive therapeutic approach for diabetes management.
[Consideration]
Choline oleate functions as a surfactant within the microemulsion system and cooperates with the oil phase and co-surfactant to disrupt the stratum corneum barrier and thereby enhancing skin permeability. It is likely to interact with the lipid components of the stratum corneum, leading to increased lipid fluidity of the highly ordered lamellar structure. Meanwhile, the choline-based internal polar phase serves as an effective solvent for GLP-1 RAs, maintaining peptide structural stability and reducing their interactions with extracellular matrix (ECM) components. This reduction in interaction is expected to facilitate diffusion through the dermal layer and promote subsequent systemic absorption.
[Conclusion]
These findings demonstrate that the IL-based microemulsion system enables sustained transdermal delivery of GLP-1 RAs. Following topical application, GLP-1 RAs are gradually released and may be transiently retained within subcutaneous tissues, allowing prolonged diffusion into systemic circulation. In addition, the high binding affinity of GLP-1 RAs to plasma proteins contributes to an extended systemic half-life. Overall, this delivery platform represents a promising non-invasive strategy for the treatment of diabetes mellitus.
Diabetes mellitus is a chronic condition characterized by persistently high blood glucose levels. Obesity, a major risk factor for diabetes, continues to rise worldwide. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for treating type 2 diabetes mellitus and obesity by mimicking the effects of the endogenous GLP-1 hormone, which regulates glucose-dependent insulin secretion. However, GLP-1 RAs are primarily administered via injection, which places a significant burden on patients. To improve patient quality of life, we focused on transdermal drug delivery, which offers a non-invasive alternative.
[Method]
Ionic liquids (ILs), defined as organic salts with melting points below 100 °C, have attracted increasing attention as drug delivery enhancers. Choline-based ILs exhibit favorable biocompatibility, structural tunability, and the ability to enhance peptide solubility and skin permeability. In this study, we developed an IL-based microemulsion system as a novel strategy to overcome the skin barrier and reduce the limitations associated with conventional GLP-1 RA administration.
[Results]
Based on the optimized formulation, nanoparticles with an average diameter of approximately 20 nm were successfully prepared and exhibited good stability at room temperature. In vitro Franz diffusion cell experiments demonstrated that the developed system significantly enhanced the transdermal permeation of GLP-1 RAs. Enhanced penetration into deeper skin layers was further confirmed by CLSM imaging. Furthermore, in vivo studies revealed a sustained and stable reduction in blood glucose levels, highlighting the potential of this system as a non-invasive therapeutic approach for diabetes management.
[Consideration]
Choline oleate functions as a surfactant within the microemulsion system and cooperates with the oil phase and co-surfactant to disrupt the stratum corneum barrier and thereby enhancing skin permeability. It is likely to interact with the lipid components of the stratum corneum, leading to increased lipid fluidity of the highly ordered lamellar structure. Meanwhile, the choline-based internal polar phase serves as an effective solvent for GLP-1 RAs, maintaining peptide structural stability and reducing their interactions with extracellular matrix (ECM) components. This reduction in interaction is expected to facilitate diffusion through the dermal layer and promote subsequent systemic absorption.
[Conclusion]
These findings demonstrate that the IL-based microemulsion system enables sustained transdermal delivery of GLP-1 RAs. Following topical application, GLP-1 RAs are gradually released and may be transiently retained within subcutaneous tissues, allowing prolonged diffusion into systemic circulation. In addition, the high binding affinity of GLP-1 RAs to plasma proteins contributes to an extended systemic half-life. Overall, this delivery platform represents a promising non-invasive strategy for the treatment of diabetes mellitus.
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