Transdermal Delivery of Chinese Medicinal Formula Mitigates Pediatric Constipation by Modulating Intestinal Endocrine and Metabolic Homeostasis.

Pediatric constipation, attributed to the functional immaturity of the gastrointestinal tract in children, is a common clinical disorder characterized by impaired gastrointestinal motility and infrequent bowel movements. Existing therapeutic strategies are frequently constrained by suboptimal efficacy owing to their single-target mechanisms and systemic toxicity. In contrast, Chinese medicinal formulas, with their multicomponent and multitarget intervention strategies, offer a highly suitable alternative for managing constipation. The traditional Chinese medicine formula "YiNianJin" (YNJ) is composed of cinnabar, rhubarb, stir-fried morning glory seeds, areca nut, and ginseng. It has demonstrated significant therapeutic efficacy in accelerating intestinal peristalsis through the synergistic regulation of aquaporin expression and the release of endocrine homeostatic transmitters. However, the clinical application of YNJ is significantly limited by conventional oral administration, which leads to Hg2+ accumulation and the low bioavailability of the active components. To address these challenges, we developed a sustained-release transdermal patch named YNJ patch (YNJP), which encapsulates cinnabar-loaded nanovesicles along with other active constituents in carboxymethyl cellulose sodium matrix. YNJP was shown to significantly enhance intestinal motility (as evidenced by a 24.02% increase in propulsion rate) by regulating the expression of mucin 2, aquaporin 3, and tight junction protein 1, while simultaneously promoting the release of endocrine homeostatic transmitters and Lactobacilli-mediated short-chain fatty acids. Therefore, YNJP is shown as a novel transdermal platform that alleviates pediatric constipation by modulating intestinal endocrine and metabolic homeostasis, enabling safe delivery of complex formulas with strong clinical potential for complex disorders.