Pharmacokinetics of Jiaotai pill self-microemulsion in insomnia rats

Objective:The pharmacokinetics and relative bioavailability of Jiaotai pill self-microemulsion were evaluated by investigating the blood concentration of Berberine,Coptisine,Palmatine and Jatrorrhizine in insomnia rats.Methods:Insomnia rat model was established by intraperitoneal injection of p-chlorophenylalanine(PCPA).The model rats were given Jiaotai pill self-microemulsion and Jiaotai pill suspension.The contents of Berberine,Coptisine,Palmatine and Jatrorrhizine in plasma at different times after administration were determined by UPLC-MS/MS,and calculate pharmacokinetic parameters.Results:Under the set chromatographic conditions,the linear relationship of the four components was good,and the precision,accuracy and stability meet the requirements of biological samples.After intragastric administration of Jiaotai pill self-microemulsion,The C_(max) of Berberine,Coptisine,Palmatine and Jatrorrhizine were(412.68±28.45),(68.65±3.92),(34.06±3.13),(40.60±1.22)ng/mL,and AUC_(0-∞)were(672.70±72.55),(146.04±25.01),(71.49±18.67),(72.25±9.54)ng·mL^(-1)·h^(-1),respectively.Compared with Jiaotai pill suspension,the Cmax,AUC_(0-t) and AUC_(0-∞)of the four components in insomnia rats were significantly increased(P<0.01).Conclusion:Jiaotai pill self-microemulsionl can promote the absorption of effective components in insomnia rats and improve its bioavailability.

Experimental study of Quercetin self-nanoemulsifying drug delivery system in inhibiting SMMC-7721 cells

Objective： To study the mechanism of inhibition of SMMC-7721 liver cancer cells by quercetin self-nanoemulsifying drug delivery system （Q-SNEDDS） in vitro. Methods： The inhibitory effect of Q-SNEDDS on hepatoma cells was detected by MTT assay. The effect of Q-SNEDDS on apoptosis of hepatoma cells was detected by flow cytometry. The changes of Q-SNEDDS after hepatoma cells were observed by fluorescence microscopy. The effect of Q-SNEDDS on the expression of signal tra_nsduction and activator of transcription 3 （STAT3） and a_nti-apoptotic factor （survivin） protein in hepatoma cells was examined by Immunohistochemistry. Results： Q-SNEDDS significantly inhibited the proliferation of hepatoma cells in a concentration-dependent manner. After 24 h of Q-SNEDDS treatment, the total apoptosis rate was 25.8%; STAT3 and survivin protein expression was down-regulated in the Q-SNEDDS group. Conclusion： Q-SNEDDS may play a role in inducing apoptosis by inhibiting the expression of STAT3 and survivin proteins.

Self-microemulsifying drug delivery system for improving the bioavailability of huperzine A by lymphatic uptake

Huperzine A(Hup-A) is a poorly water-soluble drug with low oral bioavailability. A selfmicroemulsifying drug delivery system(SMEDDS) was used to enhance the oral bioavailability and lymphatic uptake and transport of Hup-A. A single-pass intestinal perfusion(SPIP) technique and a chylomicron flow-blocking approach were used to study its intestinal absorption, mesenteric lymph node distribution and intestinal lymphatic uptake. The value of the area under the plasma concentration–time curve(AUC) of Hup-A SMEDDS was significantly higher than that of a Hup-A suspension(P <0.01).The absorption rate constant(K_a) and the apparent permeability coefficient(P_(app)) for Hup-A in different parts of the intestine suggested a passive transport mechanism, and the values of K_a and P_(app) of Hup-A SMEDDS in the ileum were much higher than those in other intestinal segments. The determination of Hup-A concentration in mesenteric lymph nodes can be used to explain the intestinal lymphatic absorption of Hup-A SMEDDS. For Hup-A SMEDDS, the values of AUC and maximum plasma concentration(C_(max)) of the blocking model were significantly lower than those of the control model(P<0.05). The proportion of lymphatic transport of Hup-A SMEDDS and Hup-A suspension were about 40% and 5%,respectively, suggesting that SMEDDS can significantly improve the intestinal lymphatic uptake and transport of Hup-A.