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

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 (R) were utilized as both preand 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 pretreatment 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.