Abstract
Hyaluronic acid (HA) is widely adopted to fabricate dissolving microneedles for transdermal drug delivery applications, yet the structure-activity relationship between molecular weight of HA and transdermal delivery efficiency of microneedles (HA-MNs) has not been fully explored, particularly in the transdermal delivery of small molecule drugs. Herein, we report the fabrication of three types of HA-MNs of various molecular weights (10k, 74k and 290k Da), which incorporate rhodamine B as the model drug. We assess the influence of molecular weight of HA on the mechanical properties of HA-MNs and transdermal delivery of rhodamine B in vitro and in vivo. The mechanical strength of all types of HA-MNs exceeds the minimal force requirement for skin penetration, with the highest values of compression force found in 10k-HA-MN. Interestingly, 74k-HA-MN that owns a medium mechanical strength, exhibits the highest efficiency in transdermal delivery of rhodamine B in a porcine skin and a Franz cell transdermal model. Further in vivo fluorescence imaging of HA-MN-treated mice reveals a tunable transdermal delivery of rhodamine B, which is controllable according to the molecular weight of HA. Importantly, 74k-HA-MN treatment demonstrates the highest initial delivering amount and longest retention time of rhodamine B in mice. In addition, histological examinations of puncture sites of the skin tissues confirm the complete recovery of skin and excellent biocompatibility of HA-MNs.
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