(181ab) Rapid and Complete Implantation of Layer-By-Layer Microneedle Drug Films for Enhanced Transdermal Vaccination

He, Y., MIT
Hong, C., MIT
Li, J., Massachusetts Institute of Technology
Howard, M., MIT
Li, Y., MIT
Turvey, M., Singapore-MIT Alliance for Research and Technology
Uppu, D., Singapore-MIT Alliance for Research and Technology
Martin, J., MIT
Zhang, K., MIT
Irvine, D., MIT
Rapid and Complete Implantation of Layer-by-Layer Microneedle Drug Films for Enhanced Transdermal Vaccination

Yanpu He1,2,#, Celestine Hong1,2,#, Jiahe Li1,2, MayLin T Howard1,2, Yingzhong Li1,3, Michelle E Turvey4, Divakara SSM Uppu4, John R Martin1,2, Ketian Zhang1,5, Darrell J Irvine1,3,5,6, and Paula T Hammond1,2*

1Koch Institute for Integrative Cancer Research, 2Department of Chemical Engineering, 3Department of Biological Engineering, 5Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States. 4Infectious Diseases Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology (SMART), Singapore, Singapore. 6Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, United States.


The utility of layer-by-layer (LbL) coated microneedle (MN) skin patches for transdermal drug delivery has been proven a promising approach, with advantages over hypodermal injection due to painless and easy self-administration. However, the long epidermal application time required for drug implantation by existing LbL MN strategies (15 to 90 minutes) can lead to potential medication noncompliance. Here, we developed a MN platform to shorten the application time in MN therapies based on a synthetic pH-induced charge-invertible polymer, requiring only 1-minute skin insertion time to implant LbL films in vivo. Following MN-mediated delivery of 0.5 μg model antigen chicken ovalbumin (OVA) in the skin of mice, this system achieved sustained release over 3 days and led to an elevated immune response as demonstrated by significantly higher humoral immunity compared with OVA administration via conventional routes (subcutaneously and intramuscularly). Serum OVA-specific IgG1 level of the microneedle vaccinated group was 9-fold and 160-fold higher than that in intramuscular and subcutaneous injection groups, respectively. Moreover, in an ex vivo experiment on human skin surgical samples, we achieved efficient immune activation through MN-delivered LbL films, demonstrated by a rapid uptake of vaccine adjuvants by the antigen presenting cells, suggesting the potential of applying this technology to human transdermal vaccination. In addition, future work may also incorporate nucleic acid-based vaccines (e.g., mRNA), immune adjuvants (e.g., CpG oligodeoxynucleotides), or immune checkpoint inhibitors (e.g., anti-programmed cell death protein 1) into this system to compare against current delivery technologies.


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