APMAdvances in Precision Medicine2424-85922424-9106Bio-Byword Scientific Publishing Pty. Ltd.10.26689/APM.v11i6.15130ArticleConstruction and Transdermal Absorption Characteristics of Kongmian Shuibao Melatonin Transdermal Nano-Delivery System for Overcoming the First-Pass Effecthttps://artdesignp.com/journal/APM/11/6/10.26689/APM.v11i6.15130YanJesse20261162026-06-26Oral administration of melatonin is severely limited by significant hepatic first-pass metabolism, low bioavailability, and high pharmacokinetic variability. To overcome these limitations, the Yixintang Kongmian Shuibao team developed a novel melatonin nano-composite formulation with an ultra-small particle size (10–15 nm). In vitro transdermal permeability across excised male Sprague-Dawley rat skin was evaluated using Franz diffusion cells, with melatonin concentrations quantified via high-performance liquid chromatography (HPLC). The nano-composite demonstrated significantly higher transdermal absorption profiles compared to conventional oral and benchmark formulations, achieving therapeutically effective doses required for human sleep regulation. Furthermore, a 7-day repeated dermal application study in rabbits confirmed zero incidence of erythema or edema, establishing superior skin compatibility. This nano-delivery system represents a highly promising non-invasive transdermal candidate for sleep improvement.Melatonin,Transdermal nano-delivery system,Hepatic first-pass effect,In vitro permeation,Skin irritation,Bioavailability

[1] Zhang L, Wang Y, Liu H, et al., 2022, Physiological activities of melatonin and its regulatory mechanisms in oxidative stress and sleep modulation. Basic Medicine and Clinical Clinics, 42(5): 710-715. [2] Williams AC, Barry BW, 2012, Penetration enhancers and transdermal delivery of macromolecular drugs. Advanced Drug Delivery Reviews, 64: 128-137. [3] Gupta S, Kesarla R, Omri A, 2013, Formulation strategies to improve the bioavailability of poorly water-soluble drugs using lipid-based nano-carriers (10–15nm). International Journal of Pharmaceutics, 453(1): 115-125. [4] OECD, 2004, Test No. 428: Skin Absorption: In Vitro Method. OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris, 2004. [5] Hadgraft J, Lane ME, 2005, Mathematical modeling of skin absorption and transdermal drug accumulation ($Q_s$). Journal of Pharmaceutical Sciences, 94(12): 2595-2601. [6] OECD, 2015, Test No. 404: Acute Dermal Irritation/Corrosion. OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris.