Publications by authors named "Shenshen Yang"

17 Publications

  • Page 1 of 1

Study on Hepatotoxicity of Rhubarb Based on Metabolomics and Network Pharmacology.

Drug Des Devel Ther 2021 4;15:1883-1902. Epub 2021 May 4.

Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China.

Background: Rhubarb, as a traditional Chinese medicine, is the preferred drug for the treatment of stagnation and constipation in clinical practice. It has been reported that rhubarb possesses hepatotoxicity, but its mechanism in vivo is still unclear.

Methods: In this study, the chemical components in rhubarb were identified based on UPLC-Q-TOF/MS combined with data postprocessing technology. The metabolic biomarkers obtained through metabolomics technology were related to rhubarb-induced hepatotoxicity. Furthermore, the potential targets of rhubarb-induced hepatotoxicity were obtained by network pharmacology involving the above components and metabolites. Meanwhile, GO gene enrichment analysis and KEGG pathway analysis were performed on the common targets.

Results: Twenty-eight components in rhubarb were identified based on UPLC-Q-TOF/MS, and 242 targets related to rhubarb ingredients were predicted. Nine metabolic biomarkers obtained through metabolomics technology were closely related to rhubarb-induced hepatotoxicity, and 282 targets of metabolites were predicted. Among them, the levels of 4 metabolites, namely dynorphin B (10-13), cervonoyl ethanolamide, lysoPE (18:2), and 3-hydroxyphenyl 2-hydroxybenzoate, significantly increased, while the levels of 5 metabolites, namely dopamine, biopterin, choline, coenzyme Q9 and P1, P4-bis (5'-uridyl) tetraphosphate significantly decreased. In addition, 166 potential targets of rhubarb-induced hepatotoxicity were obtained by network pharmacology. The KEGG pathway analysis was performed on the common targets to obtain 46 associated signaling pathways.

Conclusion: These data suggested that rhubarb may cause liver toxicity due to its action on dopamine D1 receptor (DRD1), dopamine D2 receptor (DRD2), phosphodiesterase 4B (PDE4B), vanilloid receptor (TRPV1); transient receptor potential cation channel subfamily M member 8 (TRPM8), prostanoid EP2 receptor (PTGER2), acetylcholinesterase (ACHE), muscarinic acetylcholine receptor M3 (CHRM3) through the cAMP signaling pathway, cholinergic synapses, and inflammatory mediators to regulate TRP channels. Metabolomics technology and network pharmacology were integrated to explore rhubarb hepatotoxicity to promote the reasonable clinical application of rhubarb.
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http://dx.doi.org/10.2147/DDDT.S301417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106470PMC
May 2021

Efficient FPGA implementation of high-speed true random number generator.

Rev Sci Instrum 2021 Feb;92(2):024706

State Key Laboratory of Quantum Optics and Quantum Optics Devices, Institute of Opto-Electronics, Shanxi University, Taiyuan 030006, China and Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan 030006, China.

High-speed true random number generator is a building block in the modern information security system. We propose and demonstrate an efficient high-speed true random number generator based on multiple parallel self-timed rings (STRs). To improve the security, we evaluate the randomness of the entropy source by min-entropy and exploit the information-theoretically provable Toeplitz-hashing extractor. To minimize the consumption of hardware resources of a field programmable gate array at a predetermined high throughput and maximize the throughput with the limited hardware resources, we systematically derive and investigate the dependence of the data throughput and the total consumed resources of the random number generator on the system parameters. On this basis, we make a joint optimization for the degree of parallelism of the STRs and the extraction efficiency of the extractor. A 10-Gbps true random number generator is implemented efficiently, so that the output random bits can pass all the National Institute of Standards and Technology (NIST) and Dieharder test suites.
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http://dx.doi.org/10.1063/5.0035519DOI Listing
February 2021

Cleavage rules of mass spectrometry fragments and rapid identification of chemical components of Radix Paeoniae Alba using UHPLC-Q-TOF-MS.

Phytochem Anal 2021 Jan 27. Epub 2021 Jan 27.

School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Introduction: Radix Paeoniae Alba (RPA) presents several pharmacological effects, including analgesia, liver protection, and toxicity reduction. RPA consists mostly of monoterpenes and their glycosides, tannins, flavonoids, and organic acids, with monoterpenes being the main active pharmaceutical ingredients.

Objective: To establish an effective method for rapid classification and identification of the main monoterpenes, flavonoids, and organic acids in RPA.

Methods: We used ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) and data post-processing technology to rapidly classify and identify the monoterpenoids, flavonoids, and organic acids in RPA. We also summarised the diagnostic product ions and neutral losses of monoterpenoids, flavonoids, and organic acids in RPA reported in the literature.

Results: We identified 24 components, namely 18 monoterpenoids, one flavonoid, and five organic acids.

Conclusion: In this study, we analysed the chemically active pharmaceutical ingredients and assessed the quality of RPA. In addition, we demonstrated that UHPLC-Q-TOF-MS can be used to qualitatively classify and identify the variety of chemical components of traditional Chinese medicines (TCMs) to a certain extent. Moreover, we confirmed that mass spectrometry can be used to identify the components of TCMs.
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http://dx.doi.org/10.1002/pca.3029DOI Listing
January 2021

HTBPI, an active phenanthroindolizidine alkaloid, inhibits liver tumorigenesis by targeting Akt.

FASEB J 2020 09 24;34(9):12255-12268. Epub 2020 Jul 24.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Akt, a crucial protein involved in a variety of signaling pathways in cancer, acts as an important regulator of survival in hepatocellular carcinoma (HCC), and provides curative option for the related drugs development. We have found an active phenanthroindolizidine alkaloid, (13aR,14R)-9,11,12,13,13a,14-hexahydro-3,6,7-trimethoxydibenzo[f,h]pyrrolo[1,2-b]isoquinolin-14-ol (HTBPI), is a promising Akt inhibitor effective in the suppression of HCC cells proliferation through stimulating apoptotic and autophagic capability in vivo and in vitro. Treatment of HTBPI combined with a classical autophagy-lysosomal inhibitor (bafilomycin A1), could enhance stimulation effects of apoptosis on HCC cell lines. In addition, we confirmed HTBPI targeting Akt, occupied the kinase binding domain (Thr 308) of Akt to inactivate its function by CETSA and DARTS assay. In contrast, ectopic Akt-induced overexpression significantly abrogated inhibitory effects of HTBPI on cell viability and proliferation. Furthermore, high p-Akt (Thr 308) expression is collated with liver tumor formation and poor survival in HCC patients. In conclusions, HTBPI impeded HCC progress through regulation of apoptosis and autophagy machinery via interaction with p-Akt (Thr 308). This may provide potential molecular candidate by targeting Akt for the therapy of HCC patients.
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http://dx.doi.org/10.1096/fj.202000254RDOI Listing
September 2020

Cellular senescence and cancer: Focusing on traditional Chinese medicine and natural products.

Cell Prolif 2020 Oct 3;53(10):e12894. Epub 2020 Sep 3.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Cancer is the principal cause of death and a dominant public health problem which seriously threatening human life. Among various ways to treat cancer, traditional Chinese medicine (TCM) and natural products have outstanding anti-cancer effects with their unique advantages of high efficiency and minimal side effects. Cell senescence is a physiological process of cell growth stagnation triggered by stress, which is an important line of defence against tumour development. In recent years, active ingredients of TCM and natural products, as an interesting research hotspot, can induce cell senescence to suppress the occurrence and development of tumours, by inhibiting telomerase activity, triggering DNA damage, inducing SASP, and activating or inactivating oncogenes. In this paper, the recent research progress on the main compounds derived from TCM and natural products that play anti-cancer roles by inducing cell senescence is systematically reviewed, aiming to provide a reference for the clinical treatment of pro-senescent cancer.
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http://dx.doi.org/10.1111/cpr.12894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574878PMC
October 2020

Alkaloids from Traditional Chinese Medicine against hepatocellular carcinoma.

Biomed Pharmacother 2019 Dec 23;120:109543. Epub 2019 Oct 23.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. Electronic address:

Hepatocellular carcinoma (HCC) has become one of the major diseases that are threatening human health in the 21st century. Currently there are many approaches to treat liver cancer, but each has its own advantages and disadvantages. Among various methods of treating liver cancer, natural medicine treatment has achieved promising results because of their superiorities of high efficiency and availability, as well as low side effects. Alkaloids, as a class of natural ingredients derived from traditional Chinese medicines, have previously been shown to exert prominent anti-hepatocarcinogenic effects, through various mechanisms including inhibition of proliferation, metastasis and angiogenesis, changing cell morphology, promoting apoptosis and autophagy, triggering cell cycle arrest, regulating various cancer-related genes as well as pathways and so on. As a consequence, alkaloids suppress the development and progression of liver cancer. In this study, the mechanisms of representative alkaloids against hepatocarcinoma in each class are described systematically according to the structure classification, which mainly divides alkaloids into piperidine alkaloids, isoquinoline alkaloids, indole alkaloids, terpenoids alkaloids, steroidal alkaloids and other alkaloids. Besides using them alone, synergistic effects created together with other chemotherapy drugs and some special preparation methods also have been demonstrated. In this review, we have summarized the potential roles of several common alkaloids in the prevention and treatment of HCC, by revising the preclinical studies, highlighting the potential applications of alkaloids when they function as a therapeutic choice for HCC treatment, and integrating them into clinical practices.
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http://dx.doi.org/10.1016/j.biopha.2019.109543DOI Listing
December 2019

Modulating the Tumor Microenvironment via Oncolytic Viruses and CSF-1R Inhibition Synergistically Enhances Anti-PD-1 Immunotherapy.

Mol Ther 2019 01 17;27(1):244-260. Epub 2018 Nov 17.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, China. Electronic address:

Immunotherapy based on the immune checkpoint blockade has emerged as the most promising approach for cancer therapy. However, the proportion of colorectal cancer patients who benefit from immunotherapy is small due to the immunosuppressive tumor microenvironment. Hence, combination immunotherapy is an ideal strategy to overcome this limitation. In this study, we developed a novel combination of CSF-1R (colony-stimulating factor 1 receptor) inhibitor (PLX3397), oncolytic viruses, and anti-PD-1 antibody. Our results demonstrated that the triple treatment synergistically conferred significant tumor control and prolonged the survival of mouse models of colon cancer. Approximately 43% and 82% of mice bearing the CT26 and MC38 tumor, respectively, survived long term following the triple treatment. This combination therapy reprogrammed the immunosuppressive tumor microenvironment toward a CD8 T cell-biased anti-tumor immunity by increasing T cell infiltration in the tumor and augmenting anti-tumor CD8 T cell function. Our results provide a robust strategy for clinical combination therapy.
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http://dx.doi.org/10.1016/j.ymthe.2018.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319306PMC
January 2019

A rapid classification and identification method applied to the analysis of glycosides in Bupleuri radix and liquorice by ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

J Sep Sci 2018 Oct 27;41(19):3791-3805. Epub 2018 Aug 27.

Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, P. R. China.

Bupleuri radix and liquorice are commonly used as a hepatoprotectants. Their main effective ingredients are triterpenoid saponins. It is known that the saponins in liquorice and Bupleuri radix not only promote the metabolism of sugar and lipids but also have anti-inflammatory functions and hepatoprotective effect. However, the complexity of these compounds results in difficulty in studying their pharmacodynamics and mechanism. In this study, glycosides were the main components that were identified and selected as the main research object. First, the mass spectrometry information of the main chemical components in liquorice and Bupleuri radix were collected from the literature. The characteristic fragments and neutral losses were summarized according to typical cleavage methods. Second, the samples were analysed using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry, and characteristic fragment filters and neutral loss filters were successfully applied to screen 18 saponins from Bupleuri radix and 23 saponins and nine flavonoid glycosides from liquorice. Rapid classification and identification of the main components in Bupleuri radix and liquorice were finally achieved. This method promoted the development of chemical components in Bupleuri radix and liquorice, and provided a new way for screening, classifying, and identifying target components in complex samples of metabolomics and pharmacokinetics.
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http://dx.doi.org/10.1002/jssc.201800619DOI Listing
October 2018

Rapid Classification and Identification of Chemical Components of Schisandra Chinensis by UPLC-Q-TOF/MS Combined with Data Post-Processing.

Molecules 2017 Oct 20;22(10). Epub 2017 Oct 20.

Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.

(known in Chinese as WuWeiZi, WWZ) has observable effects such as astringing the lung to stop coughs, arresting sweating, preserving semen and preventing diarrhea. The major components of WWZ include lignans, triterpenoids, organic acids and fatty acids. In this paper, a reliable method for the rapid identification of multiple components in WWZ by their characteristic fragments and neutral losses using UPLC-Q-TOF/MS technology was developed. After review of the literature and some reference experiments, the fragmentation pattern of several compounds were studied and summarized. Then, according to the corresponding characteristic fragments coupled with neutral losses in the positive or negative ion mode produced by different types of substances a rapid identification of target compounds was achieved. Finally, a total of 30 constituents of WWZ were successfully identified, including 15 lignans, nine triterpenoids, three organic acids and three fatty acids. The method established in this study not only provides a comprehensive analysis of the chemical ingredients of WWZ, providing a basis for further phytochemical studies on WWZ but also provides a more efficient way to solve the problem of identification of complex chemical constituents in traditional Chinese medicines.
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http://dx.doi.org/10.3390/molecules22101778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151474PMC
October 2017

Analysis of E. rutaecarpa Alkaloids Constituents In Vitro and In Vivo by UPLC-Q-TOF-MS Combined with Diagnostic Fragment.

J Anal Methods Chem 2016 30;2016:4218967. Epub 2016 Jun 30.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.

Evodia rutaecarpa (Juss.) Benth. (Rutaceae) dried ripe fruit is used for dispelling colds, soothing liver, and analgesia. Pharmacological research has proved that alkaloids are the main active ingredients of E. rutaecarpa. This study aimed to rapidly classify and identify the alkaloids constituents of E. rutaecarpa by using UPLC-Q-TOF-MS coupled with diagnostic fragments. Furthermore, the effects of the material base of E. rutaecarpa bioactive ingredients in vivo were examined such that the transitional components in the blood of rats intragastrically given E. rutaecarpa were analyzed and identified. In this study, the type of alcohol extraction of E. rutaecarpa and the corresponding blood sample were used for the analysis by UPLC-Q-TOF-MS in positive ion mode. After reviewing much of the literature and collected information on the fragments, we obtained some diagnostic fragments of the alkaloids. Combining the diagnostic fragments with the technology of UPLC-Q-TOF-MS, we identified the compounds of E. rutaecarpa and blood samples and compared the ion fragment information with that of the alkaloids in E. rutaecarpa. A total of 17 alkaloids components and 6 blood components were identified. The proposed method was rapid, accurate, and sensitive. Therefore, this technique can reliably and practically analyze the chemical constituents in traditional Chinese medicine (TCM).
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http://dx.doi.org/10.1155/2016/4218967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944061PMC
July 2016

Increased dissolution and oral absorption of itraconazole/Soluplus extrudate compared with itraconazole nanosuspension.

Eur J Pharm Biopharm 2013 Nov 3;85(3 Pt B):1285-92. Epub 2013 Apr 3.

School of Pharmacy, Shenyang Pharmaceutical University, China. Electronic address:

The purpose of this article was to compare the in vitro and in vivo profiles of itraconazole (ITZ) extrudates and nanosuspension separately prepared by two different methods. And it was proved truly to form nanocrystalline and amorphous ITZ characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) analysis, Fourier transform infrared spectrum (FTIR), transmission electron microscope (TEM), and scanning electron microscope (SEM). The release of ITZ/Soluplus solid dispersions with amorphous ITZ was almost complete while only 40% release was obtained with ITZ nanocrystals. The amorphous state need not to cross over the crystal lattice energy upon dissolution while the crystalline need to overcome it. In the in vivo assay, the AUC(0-t) and C(max) of ITZ/Soluplus were 6.9- and 11.6-time higher than those of pure ITZ. The formulation of the extrudate had an AUC(0-t) and C(max) similar to those of ITZ and also OH-ITZ compared with the commercial capsule (Sporanox®). The relative bioavailability values with their 95% confidence limit were calculated to be 98.3% (92.5-104.1%) and 101.3% (97.9-104.1%), respectively. The results of this study showed increased dissolution and bioavailability of the solid dispersion of Soluplus-based carrier loading ITZ prepared by HME compared with the ITZ nanosuspension prepared by wet milling.
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http://dx.doi.org/10.1016/j.ejpb.2013.03.002DOI Listing
November 2013

Preclinical evaluations of norcantharidin-loaded intravenous lipid microspheres with low toxicity.

Expert Opin Drug Deliv 2012 Dec 13;9(12):1449-62. Epub 2012 Sep 13.

Shenyang Pharmaceutical University, Department of Pharmaceutics Science, Wenhua Road 103 Shenyang 110016 Liaoning Province, People's Republic of China.

Objectives: The aim of this study was to perform a systematic preclinical evaluation of norcantharidin (NCTD)-loaded intravenous lipid microspheres (NLM).

Research Design And Methods: Pharmacokinetics, biodistribution, antitumor efficacy and drug safety assessment (including acute toxicity, subchronic toxicity, hemolysis testing, intravenous stimulation and injection anaphylaxis) of NLM were carried out in comparison with the commercial product disodium norcantharidate injection (NI).

Results: The pharmacokinetics of NLM in rats was similar to that of NI, and a non-linear correlation was observed between AUC and dose. A comparable antitumor efficacy of NLM and NI was observed in mice inoculated with A549, BEL7402 and BCAP-37 cell lines. It was worth noting that the NLM produced a lower drug concentration in heart compared with NI, and significantly reduced the cardiac and renal toxicity. The LD(50) of NLM was twice higher than that of NI. In NLM, over 80% of NCTD was loaded in the lipid phase or bound with phospholipids. Thus, NCTD was sequestered by direct contacting with body fluids and largely avoided distribution into tissues, consequently leading to significantly reduced cardiac and renal toxicity.

Conclusions: These preclinical results suggested that NLM could be a useful potential carrier for parenteral administration of NCTD, while providing a superior safety profile.
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http://dx.doi.org/10.1517/17425247.2012.724675DOI Listing
December 2012

Pharmacokinetic comparisons of single herb extract of Fufang Danshen preparation with different combinations of its constituent herbs in rats.

J Pharm Biomed Anal 2012 Aug-Sep;67-68:77-85. Epub 2012 Apr 10.

Department of Pharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.

Salvianolic acid B (SAB), tanshinone IIA (TS), ginsenoside Rb₁ (Rb₁), ginsenoside Rg₁ (Rg₁) and notoginsenoside R₁ (R₁) are major active ingredients of Fufang Danshen preparation (FDP) for its protective effects on myocardial ischemia. This study investigated the pharmacokinetics of marker compounds after oral administration of single herb extract and different combinations of constitutional herbs in FDP, and explored potential herb-herb interactions among the ingredients in the multi-herb medicine. The pharmacokinetics study on the target compounds in rat plasma was performed using an optimal ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) coupled with protein precipitation method. There were no statistically significant differences in pharmacokinetic parameters of SAB, TS, Rb₁, Rg₁ and R₁ between single Radix Salvia miltiorrhiza (S. miltiorrhiza) or Radix Panax notoginsen (P. notoginseng) extract and combination treatment. While, in comparison with oral administration of P. notoginseng extract alone, the pharmacokinetic parameters (C(max), AUC(0-72 h), AUC(0-∞), Cl, V), particularly for Rb₁ and Rg₁, were significantly different after oral administration P. notoginseng extract with addition of borneol (p<0.05). The AUC(0-72 h) values of Rb₁ and Rg₁ were significantly increased 1.3-fold and 1.6-fold, respectively, after P. Notoginsen extract co-administered with borneol. The results showed that herb-herb interactions may be accounting for the different pharmacokinetic behaviors of active constituents administered in compound prescriptions versus in single-herb extracts, however, which were not significant in most cases.
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http://dx.doi.org/10.1016/j.jpba.2012.03.058DOI Listing
October 2012

A novel risperidone-loaded SAIB-PLGA mixture matrix depot with a reduced burst release: effects of solvents and PLGA on drug release behaviors in vitro/in vivo.

J Mater Sci Mater Med 2012 Feb 15;23(2):443-55. Epub 2011 Dec 15.

Department of Pharmaceutics Science, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, People's Republic of China.

The purpose of this study was to develop an in situ forming SAIB (sucrose acetate isobutyrate)-PLGA (poly (d, lactide-co-glycolide)) mixture matrix depot for sustained release of risperidone. The factors affecting the risperidone release kinetics were investigated to obtain further insight into the drug release mechanisms. The burst release in vitro was significantly reduced (4.95%) by using DMSO as solvent. And, increasing the PLGA content from 2 to 10% w/w decreased the initial release from 6.95 to 1.05%. The initial release in vivo decreased with increasing PLGA content (2.0% w/w PLGA, C(max) = 1161.7 ± 550.2 ng ml(-1); 10% w/w PLGA, C(max) = 280.3 ± 98.5 ng ml(-1)). The persistence (AUC(4-20 days)) over 20 days increased from 76.8 ± 20.7 to 362.8 ± 75.0 ng d ml(-1) by inclusion of 10% PLGA compared with the PLGA-free depot. These results demonstrate that the SAIB-PLGA mixture matrix depot could be useful as a sustained delivery system for risperidone.
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http://dx.doi.org/10.1007/s10856-011-4521-2DOI Listing
February 2012

Enhancing effects of chitosan and chitosan hydrochloride on intestinal absorption of berberine in rats.

Drug Dev Ind Pharm 2012 Jan 20;38(1):104-10. Epub 2011 Jul 20.

Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Wenhua 103, Liaoning, People's Republic of China.

Berberine chloride (BBR) is a plant alkaloid that has been used for centuries for treatment of inflammation, dysentery, and liver diseases. It is poorly absorbed from the gastrointestinal (GI) tract and its various clinical uses are limited because of its poor bioavailability. The object of the present study was to investigate the absorption enhancing effect of chitosan on BBR. Mixtures of BBR and chitosan were prepared and the absorption enhancement was investigated in rats. The results showed a dose-dependent absorption enhancement produced by chitosan. Formulations containing 0.5%, 1.5%, and 3.0% chitosan resulted in improvement of AUC(0-36 h) values by 1.9, 2.2, 2.5 times. The absorption enhancing ability of chitosan may be due to its ability to improve the BBR paracellular pathway in the intestinal tract. Chitosan hydrochloride, a salt of chitosan, was also investigated in this study. However, the addition of 2.0% and 3.3% chitosan hydrochloride to BBR solution did not produce any increase in either C(max) or AUC(0-36 h) of BBR. Subsequent solubility studies suggested that the reduced berberine chloride solubility in chitosan hydrochloride may limit the enhancement ability. This study showed that the optimum formulation producing the highest BBR absorption is the BBR solution containing 3.0% chitosan.
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http://dx.doi.org/10.3109/03639045.2011.592531DOI Listing
January 2012

Injectable nimodipine-loaded nanoliposomes: preparation, lyophilization and characteristics.

Int J Pharm 2011 May 15;410(1-2):180-7. Epub 2011 Mar 15.

Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua Road No. 103, Liaoning, Shenyang 110016, China.

The main purpose of this study was to prepare nimodipine-loaded nanoliposomes for injection and evaluate their characteristics after lyophilization. Nimodipine-loaded nanoliposomes were prepared by the emulsion-ultrasonic method with sodium cholesterol sulfate (SCS) as the regulator and then lyophilized by adding different cryoprotectants. SCS was used as a blender of regulator and surfactant and helped to prepare smaller liposomes due to the steric hindrance of the sulfate group. The results showed that nimodipine-loaded nanoliposomes with a 20:1 of egg yolk lecithin PL-100M vs. SCS ratio had a particle size of 86.8±42.007 nm, a zeta potential of -13.94 mV and an entrapment efficiency (EE) of 94.34% and could be stored for 12 days at 25°C. Because of the good bulking effect of mannitol and the preservative effect of trehalose, they were used to obtain suitable lyophilized nanoliposomes. The lyophiles containing 10% mannitol and 20% trehalose had a good appearance and a slightly altered particle size after rehydration. In addition, the lyophilized products were characterized by differential scanning calorimetry, X-ray diffraction and scanning electron microscopy, which confirmed the morphous state of trehalose, mannitol and the mixture. Trehalose could inhibit mannitol crystallization to some extent. The drug release from nanoliposomes before and after lyophilization in pH 7.4 phosphate buffer containing 30% ethanol was also examined and both profiles were found to fit the Viswanathan equation. This means that the drug release was controlled by the pore diffusion resistance.
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http://dx.doi.org/10.1016/j.ijpharm.2011.03.009DOI Listing
May 2011

Technology for improving the bioavailability of small molecules extracted from traditional Chinese medicines.

Expert Opin Drug Deliv 2009 Nov;6(11):1247-59

Shenyang Pharmaceutical University, School of Pharmacy, Department of Pharmaceutics, 103 Wenhua Road, Shenyang, Liaoning 110016, PR China.

Evidence that small molecules extracted from traditional Chinese medicines (TCMs) have beneficial effects on health is increasingly being reported in the scientific literature and these compounds are now widely recognized as potential therapeutic drugs. There have been several detailed studies of the absorption, distribution, metabolism and excretion of these compounds in rats and humans. However, some active components have low bioavailability owing to their unsuitable physicochemical and biopharmaceutical characteristics, resulting in differences in vivo. The main problem in using natural products as a source of pharmaceutical lead compounds is the need to improve the bioavailability of these compounds. This review presents and discusses the current methods used for improvement and their impact on the bioavailability of some new pharmaceutical lead compounds from TCMs.
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http://dx.doi.org/10.1517/17425240903206963DOI Listing
November 2009