Alpha-arbutin is one of the most efficient skin lightener agents, which shows the effect on reducing the pigmentation by competitively inhibiting human tyrosinase. However, alpha-arbutin has difficulty in skin permeability due to its hydrophilic property. The objective of this study was, therefore, to develop alpha-arbutin-loaded dissolving microneedles (DMNs) for improving the delivery of alpha-arbutin into the skin. The DMN patch was prepared using Gantrez™ S-97, hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone K-90 (PVP), chitosan, and their combinations. The optimal 8% alpha-arbutin-loaded DMNs, aside from Gantrez™ S-97, was successfully formulated with combination of 8% w/w HPMC and 40% w/w PVP K-90 (HPMC/PVP) at the weight ratio of 1:1. Both DMNs had 100% of penetration into porcine skin. Over 12 h of skin permeation, the flux of Gantrez™ S-97 DMNs and the HPMC/PVP DMNs were 66.21 μg/cm2/h and 74.24 μg/cm2/h, respectively. The accumulation amount of alpha-arbutin in the skin from Gantrez™ S-97 DMNs and HPMC/PVP DMNs was 107.76 μg and 312.23 μg, respectively. In comparison to the gel formulations, Gantrez™ S-97 DMNs and HPMC/PVP DMNs increase the delivery of alpha-arbutin across the skin approximately 2 and 4.7 times, respectively. In vivo studies found that alpha-arbutin-loaded HPMC/PVP DMNs delivered more alpha-arbutin into the skin than commercial cream. Moreover, the skin can reseal naturally after removal of DMNs patch without any signs of infection and remain stable in accelerated conditions for 4 weeks. Accordingly, alpha-arbutin-loaded HPMC/PVP DMNs could be a promising delivery platform for promoting trans-epidermal delivery of alpha-arbutin for skin lightening.
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We would like to thank Miss Pichsinee Choomung, Mr. Pitpiboon Srisantisuk, and Miss Thitipanchaya Panya for assistance with research and Dr. John Tigue for proofreading.
The research was supported by the Thailand Research Funds (RTA6180003) and the Research and Creative Fund, Faculty of Pharmacy, Silpakorn University.
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Aung, N.N., Ngawhirunpat, T., Rojanarata, T. et al. HPMC/PVP Dissolving Microneedles: a Promising Delivery Platform to Promote Trans-Epidermal Delivery of Alpha-Arbutin for Skin Lightening. AAPS PharmSciTech 21, 25 (2020). https://doi.org/10.1208/s12249-019-1599-1
- dissolving microneedles
- skin lightener
- inhibit tyrosinase