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Objectives We aimed to prepare novel magnolol-loaded mixed micelles (MAGM) by pluronic F127 and L61 to overcome the challenges of magnolol's poor solubility and then further improve its oral bioavailability. Methods Magnolol-loaded mixed micelles containing pluronic F127 and L61 were prepared by an organic solvent evaporation method. Physicochemical, transport experiment across Caco-2 cell monolayers and pharmacokinetic studies were performed to characterize MAG-M and to determine the final improvement of the oral bioavailability. Key findings The MAG-M solution was transparent and colourless with average size, polydispersity index and zeta potential of 228.0 ± 2.1 nm, 0.298 ± 0.012 and ±0.89 ± 0.02 mV. The micelle solution has a higher EE% and DL% of 81.57 ± 1.49% and 27.58 ± 0.53%, respectively. TEM result showed that the morphology of MAG-M was homogeneous and spherical shape. The dilution stability of MAG-M was no significant change in particle size and entrapment effi- ciency. MAG was demonstrated a sustained-release behaviour after encapsulated in micelles. MAG permeability across a Caco-2 cell monolayer was enhanced, and the pharmacokinetics study of MAG-M showed a 2.83-fold increase in relative oral bioavailability compared with raw MAG. Conclusions The mixed micelles containing pluronic F127 and L61 as drug delivery system provided a well strategy for resolving the poor solubility and bioavailability problems of MAG. [ABSTRACT FROM AUTHOR]

In this study, a novel ternary complex system (TCS) composed of baicalein, phospholipids, and Soluplus was prepared to improve the flowability and dissolution for baicalein phospholipid complex (BPC). TCS was characterized using differential scanning calorimetry (DSC), infrared spectroscopy (IR), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The flowability, solubility, oil–water partition coefficient, in vitro dissolution, and in vivo pharmacokinetics of the system were also evaluated. DSC, IR, PXRD, and SEM data confirmed that the crystal form of baicalein disappeared in BPC and TCS. Furthermore, the angle of repose of TCS of 35° indicated an improvement in flowability, and solubility increased by approximately eight-fold in distilled water when TCS was compared with BPC (41.00 ± 4.89 μg/mL vs. 5.00 ± 0.16 μg/mL). Approximately 91.24% of TCS was released at the end of 60 min in 0.5% SDS (pH = 6.8), which suggested that TCS could improve the dissolution velocity and extent. Moreover, TCS exhibited a considerable enhancement in bioavailability with higher peak plasma concentration (25.55 μg/mL vs. 6.05 μg/mL) and increased AUC0–∞ (62.47 μg·h/mL vs. 50.48 μg·h/mL) with 123.75% relative bioavailability compared with BPC. Thus, Soluplus achieved the purpose of improving the flowability and solubility of baicalein phospholipid complexes. The application of Soluplus to phospholipid complexes has great potential. [ABSTRACT FROM AUTHOR]

Triterpenoid toosendanin (TSN) exhibits potent cytotoxic activity through inducing apoptosis in a variety of cancer cell lines. However, the target and mechanism of the apoptotic effects by TSN remain unknown. In this study, we captured a specific binding protein of TSN in HL-60 cells by serial affinity chromatography and further identified it as deoxycytidine kinase (dCK). Combination of direct activation of dCK and inhibition of TSN-induced apoptosis by a dCK inhibitor confirmed that dCK is a target for TSN partially responsible for the apoptosis in HL-60 cells. Moreover, the activation of dCK by TSN was a result of conformational change, rather than auto-phosphorylation. Our results further imply that, in addition to the dATP increase by dCK activation in tumor cells, dCK may also involve in the apoptotic regulation. [ABSTRACT FROM AUTHOR]