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Microneedle Array Patch (MAP) Consisting of Crosslinked Hyaluronic Acid Nanoparticles for Processability and Sustained Release

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Abstract

Aims

Crosslinked hyaluronic acid (X-linked HA) is not suitable for making microneedles because of the low fluidity of X-linked HA hydrogel. Microneedles were fabricated using X-linked HA nanoparticles (X-linked HA-NPs) to utilize the sustained drug delivery capability of X-linked HA-NPs and to obtain the processability advantages of X-linked HA.

Method

The puncture performance of a microneedle array patch (MAP) made of crosslinked hyaluronic acid nanoparticles (X-linked HA-NP-MAP) was evaluated by insertion in vitro into porcine skin. After a predetermined attachment time, the remaining height of the X-linked HA-NP-MAP was measured to determine the dissolution rate. X-linked HA-NP-MAP and free HA-MAP containing Rhodamine B isothiocyanate-dextran were administered into the back skin of mice, and the relative fluorescent intensity in the back skin was measured over time.

Results

The puncture performance of the X-linked HA-NP-MAP was over 90%. The diameter of redispersed X-linked HA-NPs was same as that of the premolded X-linked HA-NPs. The dissolution rate was not different from that of free HA-MAP. In an in vivo experiment, X-linked HA-NP-MAP was administered into the mouse’s back skin successfully and the relative fluorescent intensity of X-linked HA-NP-MAP lasted longer than that of HA-MAP.

Conclusion

X-linked HA-NPs provide the biocompatibility, the processability of micromolding, sustained drug release, successful penetration into the skin, and relatively short insertion time for full disintegration of NPs in the skin. X-linked HA-NP-MAP can be used for various applications that require several days of sustained drug release.

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Abbreviations

Free HA:

Non-crosslinked HA

HA:

Hyaluronic acid

HA-MAP:

Microneedle array patch made of free hyaluronic acid

X-linked:

Crosslinked

X-linked HA-NP-MAP:

Microneedle array patch made of crosslinked hyaluronic acid nanoparticles

X-linked HA-NP:

Crosslinked hyaluronic acid nanoparticle

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ACKNOWLEDGMENTS AND DISCLOSURES

This work was supported by the Industrial Strategic Technology Development Program (10067809: Development of vaccine formulation and patient-convenient vaccine microneedle), funded by the Ministry of Trade, Industry & Energy (MOTIE, South Korea), and by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI15C2971, HI18C0590).

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Authors and Affiliations

  1. Department of Bionano Technology and Gachon BioNano Research Institute, Gachon University, Seongnam-si, Gyeonggi-do, Republic of Korea

    Dae-Sung Kim, Jun-Tae Choi, Yu-Ra Shin & Jung-Hwan Park

  2. Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea

    Cheong Bi Kim, Pil-gu Park, Hyemi Kim & Jae Myun Lee

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  1. Dae-Sung Kim
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  2. Jun-Tae Choi
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Correspondence to Jae Myun Lee or Jung-Hwan Park.

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Kim, DS., Choi, JT., Kim, C.B. et al. Microneedle Array Patch (MAP) Consisting of Crosslinked Hyaluronic Acid Nanoparticles for Processability and Sustained Release. Pharm Res 37, 50 (2020). https://doi.org/10.1007/s11095-020-2768-3

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  • DOI: https://doi.org/10.1007/s11095-020-2768-3

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