[Multiscale structure of small-molecule dry gels enhances stability and bioavailability of Borneolum Syntheticum]

The chemical instability of the core active components of Borneolum Syntheticum(borneol and isoborneol) is a key factor limiting its quality improvement. In this study, a series of small-molecule gelators based on a cholesterol skeleton were designed and synthesized, and the optimal gelator was selected through gelation-capacity-guided screening to construct a "Borneolum Syntheticum-gelator" dry gel self-assembly system. The preparation process of the dry gel was determined based on Borneolum Syntheticum loss rate, encapsulation efficiency, drug loading capacity, physicochemical characterization, and stability assessment. RESULTS:: showed that dry gels were successfully formed at mass ratios of 1∶1 and 3∶1(Borneolum Syntheticum to gelator 2), with minimal Borneolum Syntheticum loss(0.7% and 0.8%). Corresponding encapsulation efficiencies and drug loading capacities reached 98.86%, 98.96% and 49.76%, 74.88%, respectively. IR and SEM analyses indicated that hydrogen bonding and other intermolecular forces drove the formation of multi-level fibrous network structures, with the 3∶1 ratio producing a more compact three-dimensional architecture. XRD and DSC confirmed the masking of Borneolum Syntheticum's crystalline structure and the formation of new phases in the dry gel system, suggesting that synergistic stabilization was achieved through crystalline transformation and effective encapsulation. Both formulations exhibited excellent stability under high temperature, high humidity, and intense light. The 3∶1 dry gel was selected for pharmacokinetic studies, revealing that the active components, borneol and isoborneol, in the dry gel exhibited prolonged retention time and more stable release profiles in vivo. This study provides new insights for improving the quality of easily degradable TCM components.