Efficient Skin Delivery of Long-Acting Contraceptive from a Microneedle Patch

Introduction: Currently available contraceptive methods are not able to meet the needs of all users, leading to high rates of unintended pregnancy each year. Our team has been developing a novel contraceptive technology that utilizes microneedle (MN) patches¹ aimed at providing effective, long-term contraception, enhancing user accessibility and adherence through self-administration, and ensuring cost-effectiveness for global usage. An important feature of MN patches with biodegradable MNs is the ability of the MNs to rapidly detach from the patch backing upon insertion. In this work, we evaluate the effect of MN height on the detachability of MNs and demonstrate sustained contraceptive hormone delivery from MNs optimized for efficient needle detachment.

Methods: MNs were fabricated by casting a solution of poly (lactic-co-glycolic acid) (PLGA) and a contraceptive hormone, levonorgestrel (LNG), onto polydimethylsiloxane molds to form drug-loaded MNs, the mold allowing for a maximum MN height of 600 µm. A second casting solution of polyvinyl alcohol (PVA) and sucrose was used to form the rest of the MN patch. MN patches were imaged, and the height of drug-loaded MNs was measured. The ability of MN tips to detach upon insertion was evaluated by ex vivo pig skin insertion. An in vitro release study was conducted to determine the rate of LNG released from the MNs. We then evaluated MN detachment and drug release profile in vivo using a rat animal model. Liquid chromatography–mass spectrometry (LC-MS) was used to monitor the plasma concentration of LNG.

Results: More than 90% MN detachment was achieved in pig skin insertion using one cast only either with 8.5 or 10 µL casting amount indicating that the MN height should not exceed more the 2/3 of the total MN shaft height. A total of 6 MN patches were applied to each rat and an average of 90% MN detachment was achieved in vivo. MN patches showed release for 21 days in vitro and more than 17 days in vivo.

Conclusion: MN height is an important factor in the efficient detachment of biodegradable polymer MNs. By determining the optimal MN height, we developed MN patches with a high MN detachment rate which achieved long-term drug release both in vitro and in vivo.

Acknowledgments: This work was prepared under sub agreements funded by Family Health International (FHI 360) under Cooperative Agreements No. AID-OAA-15-00045 and 7200AA20CA0016, funded by the U.S. Agency for International Development (USAID). The content of this presentation does not necessarily reflect the views, analysis, or policies of FHI 360, or USAID, nor does the mention of trade names, commercial products, or organizations imply endorsement by FHI 360, or USAID. Mark Prausnitz is a co-founder and has a significant financial interest in Micron Biomedical. This conflict of interest is managed by the Georgia Institute of Technology.

References:

(1) Li W et al. J Control Release 2022, 347:489-499.