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



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.


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.


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.


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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Free HA:

Non-crosslinked HA


Hyaluronic acid


Microneedle array patch made of free hyaluronic acid



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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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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Correspondence to Jae Myun Lee or Jung-Hwan Park.

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Kim, D., Choi, J., 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).

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Key Words

  • crosslinked hyaluronic acid
  • microneedles
  • nanoparticles
  • processability
  • puncture performance
  • sustained release