Targeted intradermal delivery of alpha-arbutin-loaded dissolving polymeric microneedles visualized by three-dimensional Orbitrap secondary ion mass spectrometry (3D OrbiSIMS)

Li, Zhiwei; Marlow, Maria; Scurr, David; Zhu, Zheying

Abstract

Hyperpigmentation, a prevalent dermatological condition characterized by melanin overproduction, poses treatment challenges due to the hydrophilicity of alpha-arbutin, a widely utilized tyrosinase inhibitor. This study investigates the efficacy of dissolving microneedles (DMNs) in augmenting skin permeation for alpha-arbutin delivery to the targeted epidermal site. Porcine full-thickness skin was employed in a 24-hour Franz cell study, commencing with the assessment of commercial alpha-arbutin-containing products. Solid steel microneedles (CMNs) from Dermapen® were utilized as both pre- and post-treatment modalities to evaluate the influence of different applications on alpha-arbutin delivery. Additionally, alpha-arbutin-loaded polyvinylpyrrolidone-co-vinyl acetate (PVPVA) DMNs, containing 2% w/w alpha-arbutin, were fabricated and examined for their permeation-enhancing capabilities. HPLC analysis and 3D Orbitrap Secondary Ion Mass Spectrometry (OrbiSIMS) were employed to quantify and visualize alpha-arbutin in various Franz cell components. Results indicate that alpha-arbutin permeation to the skin was restricted (less than 1%) without microneedle application and significantly increased by 6-fold (4–5%) with post-treatment CMNs and DMNs, but not with pre-treatment CMNs. Notably, DMNs exhibited a more sustainable and robust capacity than post-treatment CMNs. OrbiSIMS imaging analysis revealed that DMNs visually enhance skin permeation of alpha-arbutin by delivering the compound to the basal layer of the targeted skin location. Overall, this study underscores the potential of DMNs as a promising delivery system for promoting targeted intradermal delivery of alpha-arbutin, providing a comprehensive exploration of various methodologies to identify innovative and improved microneedle approaches for alpha-arbutin permeation.

Citation

Li, Z., Marlow, M., Scurr, D., & Zhu, Z. (2024). Targeted intradermal delivery of alpha-arbutin-loaded dissolving polymeric microneedles visualized by three-dimensional Orbitrap secondary ion mass spectrometry (3D OrbiSIMS). European Journal of Pharmaceutics and Biopharmaceutics, 196, Article 114181. https://doi.org/10.1016/j.ejpb.2024.114181

• Journal Article Type: Article
• Acceptance Date: Jan 8, 2024
• Online Publication Date: Jan 14, 2024
• Publication Date: Mar 1, 2024
• Deposit Date: Jan 21, 2024
• Publicly Available Date: Jan 15, 2025
• Journal: European Journal of Pharmaceutics and Biopharmaceutics
• Print ISSN: 0939-6411
• Electronic ISSN: 1873-3441
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 196
• Article Number: 114181
• DOI: https://doi.org/10.1016/j.ejpb.2024.114181
• Keywords: Intradermal delivery; Hyperpigmentation; Alpha-arbutin; Microneedle; 3D OrbiSIMS; Skin permeation
• Public URL: https://nottingham-repository.worktribe.com/output/29842048