Rapidly separable microneedle patch for the sustained release of a contraceptive

Abstract

Women often have limited access to contraception, and barrier methods have low acceptance and a high failure rate, mostly due to incorrect use, which can result in unplanned pregnancies. Sustained-release formulations of contraceptive hormones are available, yet typically require their administration by trained personnel. Here, we report the design of a microneedle patch with rapidly separable biodegradable polylactic acid and polylactic-co-glycolic acid needles, and its application for the continuous release of levonorgestrel—a contraceptive hormone. Bubble structures between each microneedle and the patch backing allow the microneedles to efficiently penetrate skin under compression, and to snap off under shear within five seconds after patch administration. In rats, the microneedle patch was well tolerated, leaving little visible evidence of use, and maintained plasma concentrations of the hormone above the human therapeutic level for one month. Further development of the rapidly separable microneedle patch for self-administered, long-acting contraception could enable women to better control their fertility.

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Fig. 1: Design and fabrication of rapidly separable microneedle patches.
Fig. 2: Characterization of rapidly separable microneedle patches.
Fig. 3: Mechanical performance of rapidly separable microneedle patches.
Fig. 4: Application of rapidly separable microneedle patches to porcine skin ex vivo.
Fig. 5: Histological images of microneedles embedded in porcine skin ex vivo.
Fig. 6: Release of LNG from rapidly separable microneedle patches in vitro and in vivo in rats.
Fig. 7: Imaging of dye release from rapidly separable microneedle patches in vivo in female Sprague Dawley rats.

Data availability

The authors declare that all data supporting the results in this study are available within the paper and its Supplementary Information. Source data for the figures in this study are available from figshare with the identifier https://doi.org/10.6084/m9.figshare.6025748.

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Acknowledgements

We thank D. Owen, G. S. Kopf and J. Ayres of FHI 360 for valuable technical discussions and review of the manuscript, and D. Bondy and A. Troxler for administrative support. This publication is made possible by the generous support of the American people through the U.S. Agency for International Development (USAID) and was prepared under a subcontract funded by Family Health International under Cooperative Agreement No. AID-OAA-15-00045, funded by USAID. The content of this publication does not necessarily reflect the views, analysis or policies of FHI 360, USAID or the United States Government, nor does any mention of trade names, commercial products, or organizations imply endorsement by FHI 360, USAID or the United States Government.

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W.L., J.T., S.P.S. and M.R.P. designed the project. W.L. and M.R.P. wrote the manuscript, with contributions from R.N.T., J.T., M.R.F. and S.P.S. W.L., R.N.T. and J.T. performed the experiments. All authors analysed and interpreted the data.

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Correspondence to Mark R. Prausnitz.

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M.R.P. is an inventor of patents licensed to companies developing microneedle-based products, a paid advisor to companies developing microneedle-based products, and a founder/shareholder of companies developing microneedle-based products (Micron Biomedical). This potential conflict of interest has been disclosed and is managed by Georgia Tech and Emory University.

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Li, W., Terry, R.N., Tang, J. et al. Rapidly separable microneedle patch for the sustained release of a contraceptive. Nat Biomed Eng 3, 220–229 (2019). https://doi.org/10.1038/s41551-018-0337-4

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