This study was designed to reverse multidrug resistance of lung cancer cells by downregulating MDR1 genes through RNA interference (RNAi) technology. A novel biodegradable cationic polymer (PEG-b-PLG-g-PEIs, GGI) was synthesized and characterized by ¹H NMR. The particle size and zeta potential were measured by dynamic light scattering (DLS). The cell viability profile of GGI was tested by MTT method with both A549 and A549/DDP cell lines. Flow cytometry (FCM) technology was used to investigate the efficiency and intensity of delivering siRNA to cells by GGI polymer. RT-PCR and Western blot were used to detect the mRNA and P-gp expression after GGI/MDR1 siRNA transfection assay. The sensitivity of cisplatin administration after transfecting GGI/MDR1 siRNA polyplexs was performed with MTT and Annexin V-FITC/PI methods. The results suggest that the particle size and zeta potential of GGI/siRNA were 150-200 nm and 16-28 mV. GGI exhibited a lower cell cytotoxity than PEI 25K and higher efficiency of delivering siRNA, which dramatically decreased the expression of MDR1 mRNA and P-gp of A549/DDP cells and increased much sensitivity to cisplatin in A549/DDP cells. GGI holds a great potential in gene delivery as a novel cationic polymer for further investigation.

The development of pharmaceuticals has been providing many kinds of novel drug delivery systems, which are important for improving therapeutic effect and one of the most important fields in pharmaceutics. According to their application, we can generally divide the novel drug delivery systems into three categories:quickly performed drug delivery system, long-term drug delivery system and high effective drug delivery system. Some diseases, such as asthma, angina pectoris and migraine, require therapeutics urgently, and the drugs have to be absorbed in several minutes. Therefore, quickly performed drug delivery systems are developed, such as oral disintegrating tablets and nasal spray. For normal tablets and capsules, especially the drugs with short blood half life, the drug concentration in blood shows obvious peak-valley phenomenon, which reduces the therapeutic effect and requires multiple administration. To solve this problem, sustained drug release system was developed, which could release the drugs slowly and sustainably even in zero-order kinetics. The pulse drug delivery system was developed that can delayed and pulsed release drug for one or several times. This system is especially useful in the management of asthma and heart disease, which are often found in midnight or early morning when patients are in bed. Transdermal drug delivery system could release drugs sustainably and deliver the drugs through skin to blood circulation, providing long term activity. The water-insoluble drugs are difficult for pharmaceutical development, thus many methods were developed to improve the solubility and bioavailability of drugs. Although biopharmaceuticals are important for disease treatment, the application shadows by the poor stability and low bioavailability. Thus the biopharmaceutical delivery system was developed, which mainly focused on structure modification and encapsulation by carriers. Considering therapeutic effect requires interaction between drugs and their targets, it is important to deliver drugs to their targets. Therefore, targeting delivery systems were developed, which mainly based on the nanoparticles. Furthermore, on-demand release drug delivery systems are also developed with the property of environment-triggered drug release. In conclusion, the novel drug delivery systems were reviewed in this study.

In this study, 1-(3-(4-chlorophenyl)-5-methylthio-1H-1, 2, 4-triazol-1-yl)-butan-1-one discovered previously in our lab was selected as a inhibitor of human dihydroorotate dehydrogenase (HsDHODH) for structural optimization. The co-crystal of HsDHODH with the hit was obtained and analyzed for guiding the subsequent structural optimization. As a result, a series of novel triazole derivatives were designed and synthesized as potent HsDHODH inhibitors. Among them, compound (3-(4-chlorophenyl)-5-ethylthio-1H-1, 2, 4-triazol-1-yl)-furan-2-yl-methanone displayed high potency in the inhibition of HsDHODH with an IC₅₀ value of 1.50 μmol·L^-1. Meanwhile, the structure-activity relationships were analyzed based on the biological data and the co-crystal structure. These results provide a valuable reference for optimization of 1H-1, 2, 4-triazole derivatives as HsDHODH inhibitors in the future.

It has been an active approach to screen the active ingredients in traditional Chinese medicines (TCMs) according to the affinity property between small molecule compounds and biomaterials such as cells, bacteria and proteins. On the other hand, the biomaterials can be immobilized on a solid support before the screening procedure. The immobilization method not only can maintain the biological activities of biomaterials, but also have other advantages such as high efficiency, simple operation, easy to be continuous and automatic, etc. Carrier materials (solid supports) for the immobilization including silica gel, magnetic materials, hollow fiber, and the surface plasma resonance sensor chips have been used to immobilize biomaterials and successfully applied in the screening of active ingredients from TCMs. In this paper, applications of immobilization techniques in the screening of active components from TCMs were reviewed to provide a scientific reference to the future applications.

Puerarin (PUE), an isoflavone with anti-inflammation, anti-oxidation and neuroprotection effects, has been widely applied to the treatment of cardiovascular diseases in clinics in China. In the current study, we reported that the active pharmaceutical ingredient (API) of marketed products was the PUE monohydrate (PUEMH). During its supersaturated dissolution, the PUE concentration quickly reached a plateau, followed by a gradually concentration decrease to another lower plateau. In order to explore the internal mechanism of above phenomenon, the solid residues after saturated dissolution test were characterized by powder X-ray diffraction (PXRD), thermal gravity analysis (TGA) and Karl Fisher titration (KFT). PXRD suggested that a novel PUE crystal different from PUEMH formed during its dissolution, the following TGA and KFT confirmed the generation of PUE dihydrate (PUEDH) with much lower solubility. Moreover, polyvinylpyrrolidones (PVPK12, PVPK30 and PVPK90) were added in the dissolution medium to investigate their potential inhibition effects on such crystal transformation during dissolution process. We observed that polymers could inhibit the transformation from PUEMH to PUEDH and result in much higher PUE concentration level than that in pure water.

Licorice is one of the most common herbs in traditional Chinese medicine, and classified as top grade in Shen Nong Ben Cao Jing. There are three different original plants of licorice stipulated in Chinese Pharmacopeia, Glycyrrhiza uralensis Fisch., Glycyrrhiza glabra L., and Glycyrrhiza inflata Bat. However, previous investigation showed that the pharmacodynamic effects of the three licorices were quite different. It is very difficult to identify them by the classical identification methods. In order to establish a fast and effective identification method, we collected 240 licorice plants from 21 populations of 7 provinces, and amplified their ITS and psbA-trnH sequences. ITS sequences with a full length of 616 bp and psbA-trnH sequences with a full length of 389 bp were obtained separately. Using DNAMAN to analyze these sequences, 4 variable sites were found in ITS sequences and 2 ITS haplotypes were determined, and 3 variable sites were found in psbA-trnH sequences and 4 psbA-trnH haplotypes were determined. With the combination analysis of ITS and psbA-trnH sequences, the molecular identification method of original licorice was established. Using this method, 40 samples of licorice slices collected from 4 main herbal material markets in China were identified successfully. Furthermore, the contents of 2 triterpenes, 18α-glycyrrhizic acid and 18β-glycyrrhizic acid, and 4 flavonoids, liquiritin, isoliquiritin, liquiritigenin, and isoliquiritigenin in these licorice pieces were examined by HPLC and the results were analyzed using SPSS 21.0. This study provides a new method in identification of licorice, which may serve as a guideline for quality control of licorice slices.

Five cassane diterpenes were isolated from the 95% ethanol extract of the seeds of Caesalpinia bonduc (Leguminosea) by a combination of various chromatographic methods, including silica gel, Sephadex LH-20, and semi-preparative HPLC. On the basis of spectroscopic techniques, their structures were identified as 3β-acetoxy-cassa-12, 14(17), 15-trien-7β-ol (1), caesalmin C (2), caesall E (3), caesalpinin MJ (4), and 1-deacetylcaesalmin C (5). Among them, compound 1 is a new compound and 2, 4, 5 were isolated from the plant for the first time.

This study investigates the effects of metoprolol (METO) or/and pravastatin (PRAV) on the pharmacokinetics of metformin (METF) in rats. Twenty-eight male SD rats were divided into METF group, METF+METO group, METF+PRAV group and METF+METO+PRAV group. Blood samples were collected at 10, 20, 40, 60, 90, 120, 180, 240, 360, 480 and 600 min after oral administration of metformin, and concentration of metformin in plasma was determined by HPLC. Compared to the METF group, C_max of metformin was significantly decreased (P < 0.01) and MRT_0-t, t_1/2 and V were significantly increased in the METF+METO group; t_1/2 was significantly decreased in the METF+PRAV group; C_max was significantly decreased and MRT_0-t was significantly increased in the METF+METO+PRAV group. Compared to the METF+METO group, MRT_0-t of metformin was significantly decreased in the METF+METO+PRAV group. Compared to the METF+PRAV group, C_max of metformin was significantly decreased (P < 0.01), and MRT_0-t, t_1/2 and V were significantly increased in the METF+METO+PRAV group. There exist multiple drug interactions of metformin, metoprolol and pravastatin in rats.

A pre-column derivatization method combined with UHPLC-MS/MS was developed for the simultaneous determination of salidroside and tyrosol in Beagle dog plasma. After protein precipitation by acetonitrile, the liquid supernatant was treated with dansyl chloride under dark conditions at 60℃ for 30 min, and then, the sample solution was extracted using methyl tertiary butyl ether. The multiple reaction monitoring in positive ion mode was used for MS detection of the tested analytes with the specific ion transitions of m/z 534.2→372.0 for salidroside derivative, m/z 372.0→171.0 for tyrosol derivative and m/z 506.0→171.0 for arbutin derivative. The chromatograph separation was achieved on an ACQUITY UPLC^® BEH C₁₈ column (100 mm×2.1 mm, 1.7 μm) with a gradient mobile phase consisting of acetonitrile (0.1% formic acid)-water (10% acetonitrile, 0.1% formic acid) for 9 min. The assay showed a good linearity over the range of 0.02/0.1-20/10 μmol·L^-1 with a lower limit of quantitation of 0.02 and 0.1 μmol·L^-1 for salidroside and tyrosol in dog plasma, respectively. The intra-and inter-day precisions were all less than 8.68%, and the accuracy was within ±11.4%. The established method with a high sensitivity, good specificity and reliability was appropriate for simultaneous determination of salidroside and tyrosol in dog plasma and successfully applied to a pharmacokinetic study after intragastric administration of salidroside to Beagle dogs.

This study was designed to explore the impact of depression on kidney-yang deficiency in rats. Rats were repeatedly injected with hydrocortisone for 21 days to establish the depression model with kidneyyang deficiency. Tolbutamide, chlorzoxazone, theophylline, midazolam, omeprazole and dextromethorphan were used as substrates of CYP2C6, CYP2E1, CYP1A2, CYP3A2, CYP2D1, and CYP2D2 to test the depression impact on drug metabolism. Plasma concentrations of six CYP450 were determined by LC-MS/MS and used as pharmacokinetic parameters. Consequently, metabolism of theophylline, chlorzoxazone and tolbutamide were accelerated significantly in the model relative to the control (P < 0.01), but dextromethorphan, omeprazole and midazolam did not exhibit a significant difference. The present study suggests that depression with kidneyyang deficiency had a strong induction of CYP2E1 and moderate induction of CYP1A2, CYP2C6 in the rat model.