Polysaccharide-based microneedles loaded with botanical formulation for dual-pathway neuroimmune modulation in chemotherapy-induced nausea and vomiting.

Chemotherapy-induced nausea and vomiting (CINV) remain a major clinical challenge arising from neuroimmune dysregulation and limited efficacy of conventional antiemetics subjected to hepatic metabolism. Herein, we designed a carrier-free microneedle system (DZS@BMNs) by integrating Bletilla striata polysaccharide (BSP) supramolecular matrices with the botanical formulation Dai-Zhe-Shi-San (DZS) to achieve dual-pathway neuroimmune modulation. The triple-helical structure of BSP forms stable hydrogen-bonded complexes with DZS, serving simultaneously as a structural scaffold and a functional biopolymer for controlled release. The resulting microneedles exhibit programmable geometry (720 μm length, 280 μm base diameter), high mechanical strength, and biphasic diffusion kinetics-rapid epidermal permeation within 2 h followed by sustained transdermal delivery over 48 h. The system also demonstrated excellent cytocompatibility (>90% viability), negligible hemolysis (<2%), and good formulation stability. Mechanistically, DZS@BMNs suppressed serotonergic and dopaminergic signaling while downregulating key pro-inflammatory mediators, thereby achieving bidirectional neuroimmune regulation along the gut-brain axis. In a cisplatin-induced pica model, treatment with DZS@BMNs significantly reduced kaolin intake by 38% compared with dexamethasone during the acute phase, accompanied by tissue-specific reductions in serotonin levels: 42% in the brain, 38% in the ileum, and 22% in plasma. Collectively, this study presents a biofunctional polysaccharide-based microneedle system that integrates botanical pharmacology with macromolecular material engineering, offering a minimally invasive and biocompatible strategy for the management of CINV.