Optimization of Formulation of Co-loaded Docetaxel and Gambogic Acid Albumin Nanoparticles and Evaluation of Its Quality / 中国实验方剂学杂志

Objective: The formulation of co-loaded docetaxel(DTX) and gambogic acid(GA) albumin nanoparticles(DTX-GA-BSA NPs) was optimized by central composite design-response surface methodology to prepare DTX-GA-BSA NPs, and its quality was evaluated. The optimal synergistic ratio of DTX and GA was screened by coefficient of drug interaction(CDI). Method: NabTM method was used to prepare DTX-GA-BSA NPs with bovine serum albumin(BSA) as the carrier material. Design-Expert 8.0.6 software was used to design the experiment and process the data, overall desirability(OD) of particle size and polydispersity index(PDI), encapsulation rate were taken as indexes. The particle size and Zeta potential of the nanoparticles were measured. Individual and synergistic inhibitory effects of DTX and GA on the proliferation of MGC-803 and HGC-27 cells were determined by methyl thiazolyl tetrazolium(MTT) assay, respectively. Result: The optimum prescription of DTX-GA-BSA NPs was as follows:BSA concentration of 5 g·L-1, water-oil phase volume ratio of 1:17, drug-loading ratio(mass ration of drug to carrier) of 1:10.The average particle size of DTX-GA-BSA NPs was 135.8 nm and PDI was 0.09, Zeta potential was -21.4 mV. The deviation between the predicted value and the observed value of the model was small, the model had good predictability. For MGC-803 cell, when the concentrations of DTX and GA were 0.004, 0.12 μmol·L-1, respectively(mass ratio of DTX to GA was 1:23), the CDI value was the smallest and the synergistic proliferation inhibition was the most significant. For HGC-27 cell, when the concentrations of DTX and GA were 0.004, 1 μmol·L-1, respectively(mass ratio of DTX to GA was 1:195), the synergistic proliferation inhibition was the most significant. Conclusion: The optimized formulation of DTX-GA-BSA NPs is stable and reliable. The established mathematical model has good predictive ability and practicability. DTX combined with GA has synergistic effect on MGC-803 and HGC-27 cells without concentration dependence.

Gastrointestinal Regulation of Red Yeast Rice on Mice with Syndrome of Food Retention Due to Spleen Deficiency Before and After Fermentation / 中国实验方剂学杂志

Objective: To investigate gastrointestinal regulation of red yeast rice on spleen deficient dyspepsia mice, and provide reference for clarifying mechanism of invigorating spleen to promote digestion of fermented traditional Chinese medicine. Method: Mice were randomly divided into 5 groups, including the blank group, the model group, the unfermented red yeast rice treatment group (1.17 g·kg-1·d-1), the fermented red yeast rice treatment group (1.17 g·kg-1·d-1), the domperidone group (3.9 mg·kg-1·d-1), ten mice in each group were continuous intragastric administration for 10 days. The effects of red yeast rice before and after fermentation on the general behavior, body weight, food intake and gastrointestinal function of spleen deficient dyspepsia mice were compared. The effects of red yeast rice on the gastrointestinal hormone[motilin (MTL), gastrin (GAS), 5-hydroxytryptamine (5-HT), vasoactive intestinal peptide (VIP)] levels in serum of spleen deficient dyspepsia mice were determined by enzyme-linked immunosorption assay (ELISA). The regulation function of red yeast rice on the pathological changes of gastrointestinal tissue of spleen deficient dyspepsia mice was investigated by hematoxylin-eosin (HE) staining. The effect of red yeast rice on gut microbiota of spleen deficient dyspepsia mice was investigated, the primers were designed on bacterial 16S rRNA V3-V4 region sequences and Illumina Miseq platform was used for high-throughput sequencing. Result: Compared with the model group, fermented red yeast rice could recover the body weight and food intake, reduce gastric residual rate (PPEscherichia-Shigella, while increasing the relative abundance of the beneficial bacteria such as Lactobacillus and Bifidobacterium. Conclusion: Fermented red yeast rice can enhance the gastrointestinal function of spleen deficient dyspepsia mice, the mechanism may be related to regulating gastrointestinal hormone level, improving histopathology of gastrointestinal tissue and restoring intestinal flora structure.

Optimization of preparation procedures for nano-sponges of flavonoids fromGlycyrrhizae Radix et Rhizoma by Box-Behnken response surface methodology based on CRITIC weighted evaluation / 中国中药杂志

In this paper, nano-sponges of flavonoids from Glycyrrhizae Radix et Rhizoma (LF-NSP) were prepared by agitation-freeze drying method. Box-benhnken design and response surface method based on the single factor experiment was used to optimize the preparation process, with the stirring temperature as well as stirring time and speed as the independent variables, while with drug loading, particle size and the generalized "normalized value" as the response values. In addition, the nano-sponges were characterized by scanning electron microscope (SEM), infraredspectroscopy (FT-IR) and differential scanning calorimetry (DSC), and its release in vitro was also investigated. The results showed that the optimum preparation conditions for glycyrrhizin nano-sponges were as follows：The proportion of main drug and auxiliary drug was 1:2; the proportion of crosslinking agent DPC and β-CD was 4:1; stirring temperature 45 °C for 4.8 h at 245 r·min⁻¹. The comprehensive score of LF-NSP prepared under these conditions was 94.78. FT-IR and DSC results indicated the formation of Glycyrrhiza flavonoids nano-sponges, and SEM showed that they were spherical particles in shape. In release experiment in vitro, the cumulative release of glycyrrhizin flavonoids nano-sponges for 240 min was 81.8%, while that of crude drug was only 31.5%. Nano-sponges can significantly improve the dissolution of flavonoids from Glycyrrhizae Radix et Rhizoma.