张强
个性化签名
- 姓名:张强
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学术头衔:
博士生导师
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学科领域:
药剂学
- 研究兴趣:
张强教授,1982年毕业于原北京医学院药学系,先后在欧洲与日本学习与工作,现任北京大学药学院教授、博士生导师、药剂系主任、北京大学药学院(科研)副院长,兼中国药学会药剂专业委员会副主任委员,国家药品与食品管理局新药评审委员,天然药物与仿生药物国家重点实验室副主任,《药学学报》副主编,《Asian J Drug of Metabolism and Pharmacokinetics》副主编等。从事药剂学研究20多年, 在国内外发表论文150余篇,其中SCI收录论文25篇(最高IF值>6,总IF值>50,引用次数>50),主编、副主编或参编专著、教材12部,获2003年中国药学发展奖药剂学科奖,在纳米给药系统的研究方面获教育部提名国家科学技术奖自然科学二等奖,在多肽蛋白新型给药系统的研究方面获教育部自然科学二等奖和跨世纪优秀人才基金奖;主讲中央广播电视大学的《药剂学》;完成了新制剂研究20余项,包括4个一类新药的制剂研究、首创1种新型纳米制剂和1种新缓释片剂,研制的制剂产品产生了良好的社会经济效益;申请国内外专利5项, 涉及到纳米、控释和微乳等高新技术。
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成果数
19
【期刊论文】Transport of proteins and peptides across human cultured alveolar A549 cell monolayer
张强, Zhiying Wang, Qiang Zhang*
International Journal of Pharmaceutics 269(2004)451-456,-0001,():
-1年11月30日
An in vitro cultured monolayer system of alveolar epithelial cells was used as a model to investigate the transport pathway of the peptides and proteins, salmon calcitonin (sCT), insulin (INS), recombinant hirudin (rHAV2), and recombinant human growth hormone (rhGH), in pulmonary epithelium. Human lung adenocarcinoma A549 cells formed continuous monolayers when grown on the polycarbonate filters of Transwell plates. The transport of the peptides and proteins having MW of 3400-22,000 Da was studied under different conditions. The results showed that the apparent permeability coefficients (Papp) of these macromolecules across A549 cell monolayers ranged from 2×10−6 to 5×10−6cm s−1 and exhibited a good inverse correlation with molecular weight. No concentration, direction, or temperature dependence was observed in the permeation of sCT, INS, and rHAV2. While the Papp of rhGH in the BA direction (2.25×10−6cm s−1) was less than that in the AB direction at both concentrations (3.20×10−6 and 3.29×10−6cm s−1). The Papp values of rhGH were concentration and temperature independent in the AB direction. These findings suggest that the hydrophilic peptides and proteins used in this study, sCT, INS, rHAV2, and rhGH, appear to cross the A549 cell monolayers via a paracellular pathway by a passive diffusion mechanism.
Pulmonary absorption, Proteins and peptides, A549
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【期刊论文】pH-sensitive nanoparticles for improving the oral bioavailability of cyclosporine A
张强, Jundong Dai a, Tsuneji Nagai b, Xueqing Wang a, Tao Zhang c, Meng Meng a, Qiang Zhang a, **
International Journal of Pharmaceutics 280(2004)229-240,-0001,():
-1年11月30日
The purpose of this work was to improve the oral bioavailability of cyclosporine A (CyA) by preparation the CyA-pH sensitive nanoparticles. The CyA-pH sensitive nanoparticles were prepared by using poly (methacrylic acid and methacrylate) copolymer. The characterization and the dispersion state of CyA at the surface or inside the polymeric matrices of the nanoparticles were investigated. The in vitro release studies were conducted by ultracentrifuge method. The bioavailability ofCyAfrom nanoparticles and Neoral microemulsionwas assessed in Sprague-Dawley (SD) rats at a dose of 15mg/kg. The particle size of the nanoparticles was within the range from 37.4
Cyclosporine A, pH-sensitive nanoparticles, Poly (, methacrylic acid and methacrylate), copolymer, Neoral microemulsion, In vitro release, Oral bioavailability
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张强, Lei He, Gui-ling Wang, Qiang Zhang*
International Journal of Pharmaceutics 250(2003)45-50,-0001,():
-1年11月30日
Based on the clinical fact that paclitaxel injection (Taxol®) frequently causes hypersensitivity reactions, we prepared an alternative paclitaxel microemulsion with small particle size (17.2nm). The hypersensitivity evaluation and pharmacokinetic behavior in rats were conducted to assess the new microemulsion. The results showed that the new microemulsion was negative and the placebo Taxol® solution was positive with regard to allergic reactions. In the pharmacokinetic study, five rats were administrated Taxol® or paclitaxel microemulsion. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, 14h and paclitaxel determined by HPLC. The area under the curve (AUC) was significantly higher in the microemulsion group (34.98μg ml-1 h) than that in the Taxol group (21.98μg ml-1h). Also, the K10 was much smaller in the microemulsion group (0.57h-1) compared with the Taxol® group (1.29h-1), showing the elimination rate was much slower in the former than in the latter. Compared with Taxol®, the paclitaxel microemulsion caused less toxicity and had a longer circulation time in rats.
Paclitaxel, Microemulsion, Taxol, Cremophor EL, Hypersensitivity, Pharmacokinetics
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张强, Qiang Zhang a, Gongtie Liao b, Dapen Weic, T. Nagai d, *
International Journal of Pharmaceutics 164(1998)21-27,-0001,():
-1年11月30日
Polybutylcyanoacrylate nanoparticles of 3H labelled gentamicin were used to investigate the possibility of gentamicin nanoparticles as the drug delivery system for intracellular chemotherapy. 3H labelled gentamicin nanoparticles were incubated with mouse peritoneal macrophages or rat hepatocytes for various lengths of time. The cells were then separated from the nanoparticles and the radioactivity of 3H in the cells was measured by a liquid scintillation counter. By comparison with the gentamicin solution, the binding to nanoparticles produced a 5.34-fold increase in the uptake of gentamicin by the macrophages in 30-min incubation and 26.74-, 8.03-and 7.36-fold increase in uptake by the hepatocytes in 1-, 12-and 24-h incubation. The stabilizers used in the preparation of nanoparticles, particle size, surfactant coating and the gentamicin concentration were each found to have an effect on the uptake of the nanoparticles by both types of cells.
Gentamicin, Nanoparticles, Mouse peritoneal macrophages, Rat hepatocytes, In vitro cell uptake
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张强, Xue-qing Wang a, Jun-dong Dai a, Zhen Chen a, Tao Zhang b, Gui-min Xia b, T. Nagai c, Qiang Zhang a, *
Journal of Controlled Release 97(2004)421-429,-0001,():
-1年11月30日
The pH-sensitive cyclosporine A (CyA) nanoparticles were prepared by the solvent displacement method with enteric dissolved polymer of hydroxypropyl methylcellulose phthalate (HPMCP; including HP50 and HP55). The CyA nanoparticles were analyzed by HPLC for yield and encapsulation efficiency, dynamic light scattering for particle size and transmission electron microscopy (TEM) for morphology. The bioavailability of CyA-HP50 and CyA-HP55 nanoparticle colloids were evaluated in rats, compared with the current available CyA microemulsion (NeoralR). The bioavailability of CyA-HP55 nanoparticle colloids with various suspending agents was also investigated. The results obtained demonstrated that the pHsensitive CyA nanoparticles with a particle size of 50-60nm and encapsulation efficiency over 95% could be reproducibly prepared. The bioavailability of CyA-HP50 and CyA-HP55 nanoparticle colloids calculated by the AUC0-72 were 82.3% and 119.6%, similar to the reference of Neoral, while the bioavailability of CyA-HP55 nanoparticle colloids was found to be higher than that of CyA-HP50 nanoparticle colloids. The increase of mean residence time (MRT) and the decrease of elimination constant of the central compartment (K10) for both CyA-HP50 and CyA-HP55 nanoparticle colloids compared with the reference indicated significant sustained release of CyA from the nanoparticles. The effects of the suspending agents on the bioavailability of CyA-HP55 nanoparticles were observed, and the bioavailability decreased as the concentration of suspending agents or the viscosity of the nanoparticle colloids increased.
Cyclosporine A, pH-sensitive, Nanoparticles, Suspending agents, Oral administration, Bioavailability, Pharmacokinetics, Rats
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张强, Wan-Liang LU, a, Qiang ZHANG, *, Li ZHENG, Hua WANG, Rong-Yu LI, Li-Feng ZHANG, Wen-Bin SHEN, b and Xi-De TU b
Biol. Pharm. Bull. 27(10)1515-1520 (2004),-0001,():
-1年11月30日
Ketoprofen is a nonsteroidal anti-inflammatory drug (NSAID) orally effective in treating fever, pain, and inflammation but gastrointestinal side effects were observed. Preparation of ketoprofen β-cyclodextrin inclusion complexes was to increase the solubility and reduce the irritation. The complexes were prepared and preliminarily confirmed using X-ray diffraction and dissolution test. Antipyretic, analgesic and anti-inflammatory models were induced by 10% yeast using rabbits, 0.8% acetic acid using mice and 1% carrageenin using rats, respectively. Results showed that the dissolution rate of ketoprofen was significantly improved by complexation. X-Ray diffraction pattern of the complexes exhibited a diffuse pattern that differed from that of physical mixture of ketoprofen and b-cyclodextrin. Ketoprofen markedly inhibited the fever reactions at a single dose of 2 mg/kg as follows: 64.53% (inhibition rate%) at 1h for ketoprofen, 73.04% at 1h for ketoprofen β-cyclodextrin inclusion complexes, respectively. Alleviating pain reaction rates following a single dose of 8mg/kg at 20min were 39.25% for the inclusion complexes and 26.72% for ketoprofen, respectively. Inhibition rates to rat edema following a single dose of 5mg/kg at 1h were 39.47% for the inclusion complexes and 23.86% for ketoprofen. Results for antipyretic, analgesic and anti-inflammatory activities showed that the rapid and stronger effects were found in the treatment group of ketoprofen b-cyclodextrin inclusion complexes in comparison with those of free ketoprofen.
ketoprofen, β-cyclodextrin inclusion complex, X-ray diffraction, antipyretic, analgesic, anti-inflammatory animal model
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【期刊论文】Redetermination of 4-nitrobenzenesulfonamide
张强, Tianyan Zhou, a, Qiang Zhang, a‡, Guoshu Chen b and Zhongyuan Zhou b*
Acta Cryst. (2004). E60, o1767-o1768,-0001,():
-1年11月30日
In the crystal structure of the title compound, C6H6N2O4S, the nitro group is nearly coplanar with the aromatic ring, the dihedral angle being 1.6 (2) The overall molecular organization is stabilized by well defined intermolecular hydrogen bonds, leading to the formation of an infinite planar network structure.
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张强, Feng Zhao, MSc, Celine Loke, Sheila Clare Rankin, BPharm, Jia-Yi Guo, How Sung Lee, PhD, Tuck Seng Wu, Theresa Tan, Te-Chih Liu, MRCP (UK), Wan-Liang Lu, Yean-Teng Lim, Qiang Zhang, Boon Cher Goh, and Soo Chin Lee
2004; 76 (3): 210-9,-0001,():
-1年11月30日
Background: Commonly occurring genetic variants in CYP2C9 are known to reduce catalytic activity and are associated with enhanced patient sensitivity to warfarin. Interethnic differences in warfarin dose requirement have been described in the Asian population, and we postulate that this could be related to genetic variants of CYP2C9 that are unique to ethnic groups. Methods: We prospectively genotyped 125 patients who were receiving a stable daily warfarin dose to maintain international normalized ratio values between 2 and 3 through comprehensive sequencing of the promoter and coding regions of the CYP2C9 gene. Results: The mean weight-adjusted warfarin maintenance dose was significantly lower for Malay and Chinese subjects than Indian subjects (P<.001 and. 014, respectively). Warfarin dose negatively correlated with age (r=-0.4, P<.001) but not with sex. Multiple variants were detected in the promoter, exonic, intronic, and 3=-untranslated regions of CYP2C9, of which 16 were novel, including 7 nonsynonymous exonic variants (208G>C, 374G>A, 485C>A, 895A>G, 1144C>T, 1190A>C, and 1362G>C). CYP2C9*3, but not CYP2C9*2, was found in Chinese and Malay patients, and carriers of the CYP2C9*3 variant in Chinese (P<.01) and Indian (P<.01) patients, but not Malay patients (P=.77), required less warfarin. The influence of the novel exonic variants on warfarin dose requirement was unclear, because they were rare, but the lower warfarin dose requirement for Chinese and Malay patients existed despite omission of individuals with any coding region variants from analysis. Conclusions: Interethnic differences in warfarin dosing in Asian subjects may result from other genetic, dietary, or environmental influences; however, these novel variants in the gene warrant further characterization through functional studies. (Clin Pharmacol Ther 2004; 76:210-9.)
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【期刊论文】Gastrointestinal Absorption of Recombinant Hirudin-2 in Rats
张强, Xueying Yan, Xiangtao Wang, Xuenong Zhang, and Qiang Zhang
JPET 308: 774-779, 2004,-0001,():
-1年11月30日
To investigate the absorption of recombinant hirudin-2 (rHV2) after oral administration to rats and its possible absorption mechanism, a series of experiments were carried out. The degradation of 125|-rHV2 in the luminal contents and variant mucosal subcellular fractions, as well as the effect of degradation inhibition of some adjuvant was investigated. The bioavailability of rHV2, with or without degradation inhibitor after oral administration to rats was estimated, whereas the in situ loop test and everted sac experiment were also conducted to understand more about the gastrointestinal absorption of rHV2 in rats. It was demonstrated that the rHV2 was not stable in the luminal contents and subfraction of the intestinal mucosa. Some enzyme inhibitor, such as bacitracin or casein, could inhibit the degradation to certain degrees. The intact rHV2 molecules were found in the rat plasma after oral administration, and the bioavailability varies obviously, dependent on the analytical method. Some of the enzyme inhibitor could enhance the rHV2 oral absorption. There is no site difference on rHV2 absorption in different segments of small intestine. The possible transport mechanism of rHV2 across the gastrointestinal tract is concerned with the endocytosis process.
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张强, Wan-Liang Lu, *, a, b, c, Qiang ZHANG, How-Sung LEE, Tian-Yan ZHOU, Hua-Dong SUN, Da-Wei ZHANG, Li ZHENG, Michael LEE, d and Sai-Ming WONG d
Biol. Pharm. Bull. 26 (1) 52-55 (2003),-0001,():
-1年11月30日
Coenzyme Q10 (CoQ10), a highly lipophilic compound present in the inner mitochondrial membrane, is essential for production of cellular energy in the form of ATP. CoQ10 is used as a dietary supplement and for treatment of various cardiovascular disorders. Our goal was to compare the CoQ10 levels in Asians following multiple oral doses administered as sustained release or regular tablets. Twenty healthy male volunteers (19-23 years old) were divided into two equal groups. Each subject in Group I received 50mg oral doses of coenzyme Q10 as sustained release tablets once a day for fifteen days, while subject in Group II received 50mg doses of coenzyme Q10 regular tablets. The CoQ10 levels were measured by HPLC-UV (reverse phase ODS column, 10mm, 250×4.6mm; oven temperature 30°C). Mobile phase was constituted by methanol–ethanol 9:1 v/v. Flow ratewas 1.5 ml/min and UV detection was carried out at 275nm. Coenzyme Q9 was used as an internal standard. CoQ10 baseline in the morning was 0.88±0.48mg/l. Following 1 week 50mg/d dosing of CoQ10, plasma CoQ10 concentrations increased to 1.85±1.03mg/l for sustained release tablets and up to 1.37±0.74mg/l for regular tablets. The net increment proportion in AUC for sustained release and regular tablets were 148.26±176.56%, 102.57±130.00%, respectively. Both preparations significantly increased the systemic exposure when compared to endogenous baseline.
Coenzyme Q10, sustained release tablets, HPLC-UV, plasma concentration, Asian human healthy volunteer
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