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Supramolecular soft matter in traditional Chinese medicine: multiscale structure–function evidence, critical limitations, and translational challenges

Year: 2026

Type: article

Abstract: Plant metabolites used in traditional Chinese medicine (TCM) can form supramolecular assemblies in decoctions or in formulations prepared from purified molecules. These experimental settings support different conclusions. This narrative review examines TCM-derived supramolecular soft matter (TCM-derived SSM) through relationships among molecular interactions, assembly structure, physicochemical properties, and biological responses. It distinguishes assemblies isolated from decoctions, recombined extracts, formulations prepared from purified metabolites, and mixtures of defined metabolites with extracts. Micelles, vesicles, nanoparticles (NPs), nanofibers (NFs), and supramolecular gels provide examples, while carbonized products and covalently crosslinked carriers are discussed as related materials with distinct formation mechanisms. Selected studies associate morphology, surface chemistry, or deformability with altered delivery and preclinical activity. However, the presence of particles, successful reconstitution, and improved efficacy do not individually establish that an assembly is necessary for the effect of a complete preparation. Our contribution is an evidence-oriented comparison of preparation routes, structural measurements, biological comparisons, and the limits of inference across these preparations. We also examine artificial intelligence (AI)-assisted modeling and candidate critical quality attributes (CQAs) within a Quality by Design (QbD) perspective. Predictive design and assembly-based quality control are presented as research prospects that require reproducible measurements, appropriate controls, and validation across batches and biological settings. Self-assembly is a general physicochemical phenomenon; TCM provides a context for studying defined botanical drug combinations and preparation processes rather than evidence of properties unique to one medical tradition. We position this physical-state perspective within the established literature on synergy, antagonism and pharmacokinetic interactions in botanical mixtures.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1945675