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Preparation, characterization, and in vivo evaluation of levonorgestrel-loaded thermostable microneedles

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Abstract

To facilitate the storage and use of poly (lactic-co-glycolic acid) (PLGA)-based microneedles (MNs) in hot seasons and regions, thermally stable MNs loaded with levonorgestrel (LNG) were developed. Due to its good biocompatibility and high glass transition temperature (Tg), Hydroxypropyl methylcellulose (HPMC) was added to the PLGA-based MNs to increase thermal stability. MNs with HPMC exhibited excellent thermal stability at high temperatures. After the MNs has been applied to the skin for 10 min, the backing layer of the MNs was dissolved by contact with the interstitial fluid of skin, which resulted in the separation of the MN tips from the backing layer. The MN tips were implanted intradermally and sustained-release LNG. Biodegradable polymers were used to encapsulate the LNG, providing long-acting contraception. The in vitro release rate of LNG from the MNs reached 72.78%-83.76% within 21 days. In rats, the MNs maintained plasma concentrations of LNG above the human contraceptive level for 8–12 days. In mice, the time required for complete degradation of the MN tips was 12–16 days. MNs have excellent medication adherence due to the advantages of painlessness, minimally invasive, and self-administered. MNs can make long-acting contraceptives more readily available to humans.

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Acknowledgements

The authors are grateful to the Medical Animal Experimentation Centre of the China Academy of Chinese Medical Sciences for guiding us in conducting in vivo animal imaging.

Funding

This work was funded by the National Key Research and Development Plan of China (No. 2016YFC1000902).

Author information

Author notes

  1. Suohui Zhang and Yunhua Gao contributed equally to this work.

Authors and Affiliations

  1. Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, China

    Baorui Wang, Suohui Zhang, Xiaoyu Zhao & Yunhua Gao

  2. School of Future Technology, University of Chinese Academy of Sciences, Beijing, 101408, China

    Baorui Wang

  3. College of Investigation, Peoples Public, Security University of China, Beijing, 100038, China

    Jie Lian

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  1. Baorui Wang
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Contributions

The manuscript was written by Baorui Wang. Baorui Wang, Xiaoyu Zhao, and Jie Lian all contributed to the experiments. Suohui Zhang and Yunhua Gao supervised the project.

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Correspondence to Suohui Zhang.

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This work complies with the current laws of the country in which it was conducted. This work does not involve human subjects. All animal studies were approved by the Animal Ethics Review Committee of the Technical Institute of Physics and Chemistry, Chinese Academy of Sciences.

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Wang, B., Zhang, S., Zhao, X. et al. Preparation, characterization, and in vivo evaluation of levonorgestrel-loaded thermostable microneedles. Drug Deliv. and Transl. Res. 12, 944–956 (2022). https://doi.org/10.1007/s13346-021-01057-7

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