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Transdermal microneedles for the programmable burst release of multiple vaccine payloads

Abstract

Repeated bolus injections are associated with higher costs and poor compliance and can hinder the implementation of global immunization campaigns. Here, we report the development and preclinical testing of patches of transdermal core–shell microneedles—which were fabricated by the micromoulding and alignment of vaccine cores and shells made from poly(lactic-co-glycolic acid) with varying degradability kinetics—for the preprogrammed burst release of vaccine payloads over a period of a few days to more than a month from a single administration. In rats, microneedles loaded with a clinically available vaccine (Prevnar-13) against the bacterium Streptococcus pneumoniae induced immune responses that were similar to immune responses observed after multiple subcutaneous bolus injections, and led to immune protection against a lethal bacterial dose. Microneedle patches delivering preprogrammed doses may offer an alternative strategy to prophylactic and therapeutic protocols that require multiple injections.

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Fig. 1: Fully embedded dermal core–shell microneedles for single-administration vaccines with delayed burst release that simulate multiple bolus injections over a long period of time.
Fig. 2: In vitro delayed burst release, loading capacity and mechanical properties of core–shell microneedles.
Fig. 3: In vivo delayed burst release from the core–shell microneedles and OVA vaccination.
Fig. 4: Prevnar-13-loaded core–shell microneedle vaccination and in vivo infectious pneumococcal challenge.

Data availability

The main data supporting the results in this study are available within the paper and its Supplementary Information. All data generated in this study, including source data and the data used to generate the figures, are available at Figshare under the identifier https://doi.org/10.6084/m9.figshare.12951794.

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Acknowledgements

We thank staff at the UConn Clean room and IVIS SpectrumCT facilities for equipment support on the microfabrication and in vivo imaging, respectively; C. Schondelmeyer and staff at the University of Connecticut Animal Facility for training and support for our animal research; staff at the UConn/Thermo Fisher Scientific Center for Advanced Microscopy and Materials Analysis for SEM imaging; staff at the UConn Machine shop, K. S. Wrobel, N. Romano and A. N. Miller for making the custom-built alignment device; F. Almonte for his assistance with mechanical testing; the undergraduate students A. Johnson, K. Berkery, E. Grandell, N. Pasnoori and H. Patel for help with the fabrication process, biological experiments and measuring release time points. The initial funding of this project was provided by Bio pipeline CT and Start-up funding from University of Connecticut (USA). This work was performed in part at the Advanced Science Research Center NanoFabrication Facility of the Graduate Center at the City University of New York, USA.

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Contributions

K.T.M.T. and T.D.N. designed the concepts and research studies. K.T.M.T., S.M.S. and T.D.N. conceived the experiments. K.T.M.T., T.D.G., N.J.F., E.J.C., A.B.M., A.P., L.B., S.K., N.M. and R.P. performed the research and experiments. T.D.G., S.M.S. and T.D.N. provided reagents, advice and materials. K.T.M.T., T.D.G., S.M.S. and T.D.N. wrote the paper.

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Correspondence to Thanh D. Nguyen.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–19, Tables 1–3 and references.

Reporting Summary

Supplementary Video 1

Fabrication process for the core–shell microneedles.

Supplementary Video 2

Administration of the microneedles into rat skin using a commercial applicator.

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Tran, K.T.M., Gavitt, T.D., Farrell, N.J. et al. Transdermal microneedles for the programmable burst release of multiple vaccine payloads. Nat Biomed Eng (2020). https://doi.org/10.1038/s41551-020-00650-4

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