Melatonin, an endogenous circadian rhythm-regulating hormone, has faced challenges in achieving prolonged exogenous regulation due to its low oral bioavailability and short half-life. Existing transdermal strategies are difficult to balance efficacy, safety, and accessibility. To address this, we propose a physicochemical synergistic permeation-enhancement strategy and have developed a melatonin textile transdermal patch based on the synergistic action of electret and permeation enhancer. The patch is designed with a three-layer composite structure, composed of a textile-based electret backing layer, a drug-loading pressure sensitive adhesive layer containing melatonin and permeation enhancer, and a protective layer to prevent drug leakage. Electret and permeation enhancer enhance transdermal efficiency through a physicochemical synergistic permeation-enhancement strategy without disrupting the skin barrier. In vitro studies revealed that among various permeation enhancers (menthol, azone, oleic acid) and electret parameters, the combination of a -1500 V electret with 10% oleic acid exhibited the optimal synergistic effect. In vivo pharmacokinetic studies demonstrated that the patch reached a peak plasma concentration (>30 ng/mL) within 1 h and maintained effective therapeutic levels (>5 ng/mL) for up to 8 h. The patch significantly improved the sleep quality in insomniac rats, with no observed skin irritation or cytotoxicity. This study not only accomplishes an efficient, non-invasive, and parametrically tunable transdermal delivery of melatonin but also validates the feasibility of synergistic enhancement through physical field regulation and chemical permeation, thereby providing a viable strategy for developing safe and long-acting textile-based transdermal drug delivery systems aimed at neuroendocrine small-molecule hormones similar to melatonin.
