Dual-drug thermosensitive hydrogel-based microneedles for synchronized transdermal delivery of paeoniflorin and glycyrrhizic acid.

Efficient and synchronized co-delivery of active pharmaceutical ingredients (APIs) from classical Traditional Chinese Medicine (TCM) formulae is crucial for exerting their synergistic therapeutic effects. However, constructing dual-drug-loaded systems capable of controllably delivering APIs with divergent polarities remains challenging due to differences in molecular weight and solubility among constituents. In this study, paeoniflorin (PAE) and glycyrrhizic acid (GLA)-active ingredients derived from the renowned TCM formula Shaoyao Gancao Decoction-were selected as model compounds. To address the co-loading and synchronized delivery of hydrophilic PAE and hydrophobic GLA, we developed a β-glycerophosphate disodium salt (β-GP)/hydroxypropyl cellulose (HPC) hydrogel. This hydrogel uniquely combined skin-triggered sol-gel transition with electrostatically enhanced solubility for GLA, and was subsequently fabricated into a microneedles (MNs) formulation. Confocal laser scanning microscopy confirmed uniform distribution of both drugs within the MNs, despite their contrasting polarities. In vitro transdermal studies revealed that the MNs significantly outperformed the hydrogel in terms of delivery efficiency. Release kinetics followed the Higuchi model, with cumulative release rates at 72 h reaching 38.84 ± 0.52 % for PAE and 44.26 ± 4.38 % for GLA, indicating synchronized release. This platform represents an innovative strategy for achieving the synchronized, efficient, and sustained delivery, holding significant promise for advancing the development of TCM formulations.