Bergapten-Loaded Dissolving Microneedles for Vitiligo Treatment: A Synergistic Strategy Combining Nanocrystal...

Bergapten can effectively treat vitiligo by increasing the activity of melanocytes and tyrosinase, but its low solubility and poor transdermal effect limit its application. In this study, we used dissolvable microneedles (shells) loaded with bergapten nanocrystals (cores), a shell-nucleus-type formulation design, to treat vitiligo, organically integrating physical and pharmacological treatments, and to improve drug delivery efficiency. Firstly, bergapten was prepared into nanocrystals and screened for dissolvable microneedle matrix, and dissolvable microneedles were prepared by centrifugal spin-coating method; then, the quality studies of bergapten nanocrystals dissolvable microneedles (BP-NCs-DMNs) were carried out on the mechanical properties, in vitro solubility properties, skin puncture, and skin barrier restorative measurements and transdermal cumulative permeation experiments; finally, the pharmacological effects of bergapten dissolvable microneedles against vitiligo were verified by determining the tyrosinase (TYR), Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), and superoxide dismutase (SOD) levels using a hydroquinone-induced mouse vitiligo model. As a result, the prepared bergapten microneedles could penetrate into the skin, and the skin did not show any redness, swelling, or excessive inflammation after removing the microneedles, and they could be dissolved in vitro in about 35 min. As a result of the in vitro transdermal experiment, the cumulative transmittance of bergapten in 24 h of bergapten microneedle was 257.9 μg/cm², and the skin absorption rate of the drug was (57.15 ± 2.61) %. The hydroquinone-induced vitiligo model in mice further verified the effect of bergapten micropigmentation on skin pigmentation in mice. In this study, dissolvable bergapten microneedles were successfully established, which can significantly improve the transdermal drug delivery efficiency of bergapten and can effectively treat vitiligo disease.