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

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.

Microneedles containing cross-linked hyaluronic acid particulates for control of degradation and swelling behaviour after administration into skin.

Microneedles (MN) containing cross-linked hyaluronic acid (X-linked HA) particulates were prepared to control the degradation and swelling behaviour after transdermal drug delivery. The X-linked HA particulates were prepared by cross-linking HA chains and then passing the particulates through a sieve. Then, microneedles were prepared by micromolding method. The rheological properties of X-linked HA were studied. The penetration success rate, mechanical failure and dissolution rate of microneedles containing only hyaluronic acid (HA MN) and microneedles containing X-linked HA were compared. The delivery of fluorescein into the skin with X-linked HA MN was also observed using a confocal microscope. The size of the pulverised particulates in water ranged between 29 and 82 µm in diameter. The HA MN and X-linked HA MN were 270 µm in length. X-linked HA MN with fluorescein was inserted to a depth of 90% of the microneedle length successfully. There was no decrease in the penetration success rate for MN with up to 20% content of X-linked HA particulates. X-linked HA MN with up to 20% of particulate content did not change the dissolution time. Delay in degradation of HA, sustained drug release, and swelling behaviour of the skin layer can be obtained by X-linked HA MN.