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Microneedle patch with pure drug tips for delivery of liraglutide: pharmacokinetics in rats and minipigs

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Abstract

Transdermal delivery of peptide drugs is almost impossible with conventional penetration enhancers because of epidermal barrier function. Microneedle (MN) patches can bypass the epidermal barrier and have been developed for trans- and intradermal delivery of peptide drugs and vaccines. However, dissolving MN patches are limited by low drug loading capacities due to their small size and admixture of drug and water-soluble excipients. Furthermore, few in vivo pharmacokinetic studies, especially in large animals such as pigs, have been performed to assess post-application systemic drug exposure. Here, we developed a dissolving MN patch with pure liraglutide at the needle tips. The MN patch could load up to 2.21 ± 0.14 mg of liraglutide in a patch size of 0.9 cm2, which was nearly two orders of magnitude higher than that obtained with conventional MN patches of the same size. Raman imaging confirmed that liraglutide was localized at the MN tips. The MN had sufficient mechanical strength to penetrate the epidermis and could deliver up to 0.93 ± 0.04 mg of liraglutide into skin with a dosing variability of less than 6.8%. The MN patch delivery enabled faster absorption of liraglutide than that provided by subcutaneous (S.C.) injection, and achieved relative bioavailability of 69.8% and 46.3% compared to S.C. injection in rats and minipigs, respectively. The MN patch also exhibited similar patterns of anti-hyperglycemic effect in diabetic rats and individual variability in pharmacokinetic parameters as S.C. injection. The liraglutide MN application was well tolerated; no skin irritation was observed in minipigs except for mild erythema occurring within 4 h after once daily administration for 7 days at the same site. Our preclinical study suggests that MN patch with pure drug needle tips might offer a safe and effective alternative to S.C. injection for administration of liraglutide.

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Availability of data and materials

The datasets generated during and/or analyzed during the current study are available from the corresponding author on request.

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Acknowledgements

We thank the support of Hundred Talents Program of Sun Yat-Sen University, Guangdong Basic and Applied Basic Research Foundation and Shenzhen Science and Technology Program.

Funding

This project was mainly supported by Hundred Talents Program of Sun Yat-Sen University and partially supported by the Guangdong Basic and Applied Basic Research Foundation (Grant No.2022A1515012156), Shenzhen Science and Technology Program (Grant No. 20220817214511001).

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Authors and Affiliations

  1. School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, China

    Hongbing Lin, Jinbin Liu, Yulin Hou, Jingwen Hu & Dengning Xia

  2. Dongguan HEC Biopharmaceutical R&D Co., Ltd., Dongguan, China

    Zhiyan Yu, Juan Hong, Jianghong Yu & Yu Chen

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  1. Hongbing Lin
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  9. Dengning Xia
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D.N.X. conceived the idea; H.B.L., J.B.L., Z.Y.Y., J.H., J.H.Y., Y.C., Y.L.H., D.D.P., J.W.H. performed the experiments and analyzed the data; D.N.X. and H.B.L wrote and edited the manuscript; D.N.X. supervised the project and obtained the fundings.

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Correspondence to Dengning Xia.

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All animal experiment procedures were approved by the Institutional Animal Care and Use Committee (IACUC) of Sun Yat-sen University and Dongguan HEC Biopharmaceutical R&D Co., Ltd.

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Lin, H., Liu, J., Hou, Y. et al. Microneedle patch with pure drug tips for delivery of liraglutide: pharmacokinetics in rats and minipigs. Drug Deliv. and Transl. Res. (2024). https://doi.org/10.1007/s13346-024-01582-1

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