Poster C1 - The development of microneedle patches for subdermal mRNA lipid nanoparticle delivery

Saturday, October 26, 2024

10:00 AM - 11:00 AM EST

Location: Exhibit Hall E, F & G

Presenting Author(s)

Monica Mendoza, A.S.

Student (Undergraduate)
University of California, Berkeley
San Francisco, California, United States

Co-Author(s)

CH

Claire E. Hilburger, B.S. Bioengineering (she/her/hers)

Graduate Student
University of California, Berkeley, California, United States

Primary Investigator(s)

DD

Derfogail Delcassian, Ph.D.

Principal Investigator
University of California, Berkeley, United States

Introduction: mRNA-lipid nanoparticles (LNPs) have demonstrated clinical success as viral vaccine delivery systems. Due to the modularity of the mRNA cargo, mRNA-LNPs can be explored for therapeutic applications outside of vaccination. Here, we are developing a microneedle patch for subdermal mRNA delivery. We plan to use this mRNA patch for localized, sustained immunomodulatory mRNA delivery. Traditional mRNA-LNP vaccines are delivered to patients via intramuscular injections. However, delivery of mRNA-LNPs can be improved with the use of thermostable microneedle patches which painlessly pierce the stratum corneum and can potentially be self-applied. Additionally, this delivery mechanism could allow for the optimization of delivery rates compared to bolus injections. Here, we demonstrate the fabrication of an mRNA microneedle patch that allows for subdermal mRNA delivery in vivo.

Materials and

Methods: mRNA-LNPs were prepared by combining a lipid-containing ethanol phase with an aqueous phase containing luciferase mRNA (mLUC). Prefabricated microneedle molds were purchased to produce circular patches [160uL DI water + 40mg polymer (24% w/v PVP/PVA 50:50 stock mix)] containing mRNA-LNPs. Patches approximately 4mm in diameter were then cut in half. These microneedle patches containing mRNA-LNPs were applied in vivo to the hind paw footpads of C57/BL6 mice. Subdermal transfection was evaluated via IVIS imaging 24 hours following mRNA patch application. Data was analyzed via student’s unpaired T-test (* p< 0.05, ** p< 0.01, *** p< 0.001, ****p < 0.0001). Schematics were made with BioRender.

Results, Conclusions, and Discussions: First microneedle patches containing mRNA-LNPs were prepared in prefabricated silicon molds (Figure 1a). Patch composition, diameter, and needle length were optimized to penetrate the stratum corneum of the hind footpads of C57/BL6 mice (Figure 1b/c). We found that microneedle patches led to localized subdermal transfection (Figure 1d). At 24 hours, whole body IVIS imaging showed signal on footpads and in intramuscular injection positive control (Figure 1e). We are now optimizing patch mechanical properties to be applied subdermally to a subcutaneous melanoma lesion.

We are developing a microneedle patch for subdermal mRNA delivery. This microneedle patch could allow for localized, sustained release of mRNA-encoded cargo that is not possible with traditional bolus injections. Our next steps are to apply this patch therapeutically by delivery inflammatory cargo adjacent to a subcutaneous melanoma tumor model.

Acknowledgements (Optional):