National Pharmaceutical Engineering Research Center

Shanghai, China

National Pharmaceutical Engineering Research Center

Shanghai, China

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Wei L.,Renmin University of China | Wei L.,Hubei University | Deng W.,Renmin University of China | Deng W.,Hubei University | And 8 more authors.
Molecular Medicine Reports | Year: 2016

Hesperetin is a natural flavonoid, which has been reported to exert various biological activities and positive health effects on mammalian cells. The present study aimed to investigate the effects of hesperetin on the proliferation of primary cultured rat pulmonary artery smooth muscle cells (PASMCs), and to elucidate the possible underlying molecular mechanisms. The results of the present study indicated that hesperetin was able to inhibit the proliferation and DNA synthesis of platelet-derived growth factor-BB (PDGF-BB)-induced PASMCs in a dose- and time-dependent manner, without exerting cell cytotoxicity. In addition, hesperetin blocked the progression of the cell cycle from G0/G1 to S phase, which was correlated with the decreased mRNA expression levels of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2 and CDK4, and the increased mRNA expression levels of p27. Furthermore, the anti-proliferative effects of hesperetin were associated with suppression of the AKT/glycogen synthase kinase (GSK)3β and p38 signaling pathway, but were not associated with the extracellular signal-regulated kinases 1/2 and c-Jun N-terminal kinases signaling pathways. These results suggested that hesperetin may inhibit PDGFa-BB-induced PASMC proliferation via the AKT/GSK3β signaling pathway, and that it may possess therapeutic potential for the treatment of pulmonary vascular remodeling diseases.


Hao H.,Fudan University | Hao H.,West Anhui University | Ma Q.,National Pharmaceutical Engineering Research Center | He F.,National Pharmaceutical Engineering Research Center | Yao P.,Fudan University
Journal of Materials Chemistry B | Year: 2014

In this study, multifunctional bovine serum albumin (BSA) nanoparticles were fabricated via a green approach with high efficiency. Folic acid (FA) was conjugated to dextran (DEX) through an esterification reaction, and BSA-DEX-FA conjugate was produced by Maillard reaction. Superparamagnetic Fe3O4 nanocrystals with a size about 10 nm were loaded into BSA-DEX-FA nanoparticles through a heat treatment which induces BSA gelation. Doxorubicin (DOX) was loaded into Fe3O4/BSA-DEX-FA nanoparticles by a diffusion process. Fe3O4/BSA-DEX-FA and DOX/Fe3O4/BSA-DEX-FA nanoparticles have a size of about 100 nm, good stability, superior transversal R2 relaxation rate of larger than 360 (mM)-1 s-1, as well as FA receptor-targeted and magnetically guided functions. Fe3O4/BSA-DEX-FA nanoparticles have excellent biocompatibility. By application of an external magnetic field close to tumor, DOX/Fe3O4/BSA-DEX-FA nanoparticles can effectively enhance the tumor inhibition rate and prolong the life time of H22 tumor-bearing mice, and Fe3O4/BSA-DEX-FA nanoparticles can significantly improve the tumor MRI of KB tumor-bearing mice. This study demonstrates that Fe3O4/BSA-DEX-FA and DOX/Fe3O4/BSA-DEX-FA nanoparticles are suitable systems for tumor diagnosis and therapy. © the Partner Organisations 2014.


Deng W.,Wuhan University | Jiang D.,Wuhan University | Fang Y.,Wuhan University | Zhou H.,Wuhan University | And 8 more authors.
Journal of Molecular Histology | Year: 2013

Cardiac remodelling is a major determinant of heart failure (HF) and is characterised by cardiac hypertrophy, fibrosis, oxidative stress and myocytes apoptosis. Hesperetin, which belongs to the flavonoid subgroup of citrus flavonoids, is the main flavonoid in oranges and possesses multiple pharmacological properties. However, its role in cardiac remodelling remains unknown. We determined the effect of hesperetin on cardiac hypertrophy, fibrosis and heart function using an aortic banding (AB) mouse. Male, 8-10-week-old, wild-type C57 mice with or without oral hesperetin administration were subjected to AB or a sham operation. Our data demonstrated that hesperetin protected against cardiac hypertrophy, fibrosis and dysfunction induced by AB, as assessed by heart weigh/body weight, lung weight/body weight, heart weight/tibia length, echocardiographic and haemodynamic parameters, histological analysis, and gene expression of hypertrophic and fibrotic markers. Also, hesperetin attenuated oxidative stress and myocytes apoptosis induced by AB. The inhibitory effect of hesperetin on cardiac remodelling was mediated by blocking PKCα/βII-AKT, JNK and TGFβ1-Smad signalling pathways. In conclusion, we found that the orange flavonoid hesperetin protected against cardiac remodelling induced by pressure overload via inhibiting cardiac hypertrophy, fibrosis, oxidative stress and myocytes apoptosis. These findings suggest a potential therapeutic drug for cardiac remodelling and HF. © 2013 Springer Science+Business Media Dordrecht.


Deng W.,Renmin University of China | Deng W.,Hubei University | Fang Y.,Renmin University of China | Fang Y.,Hubei University | And 21 more authors.
Molecular Medicine Reports | Year: 2014

Cardiac remodeling is a major determinant of heart failure characterized by cardiac hypertrophy and fibrosis. Sanguinarine exerts widespread pharmacological effects, including antitumor and anti-inflammatory responses. In the present study, the effect of sanguinarine on cardiac hypertrophy, fibrosis and heart function was determined using the model induced by aortic banding (AB) in mice. AB surgery and sham surgery were performed on male wild-type C57 mice, aged 8-10 weeks, with or without administration of sanguinarine from one week after surgery for an additional seven weeks. Sanguinarine protected against the cardiac hypertrophy, fibrosis and dysfunction induced by AB, as assessed by the heart weight/body weight, lung weight/body weight and heart weight/tibia length ratios, echocardiographic and hemodynamic parameters, histological analysis, and the gene expression levels of hypertrophic and fibrotic markers. The inhibitory effect of sanguinarine on cardiac remodeling was mediated by inhibiting nuclear factor (NF)-κB signaling pathway activation. The findings indicated that sanguinarine protected against cardiac hypertrophy and fibrosis via inhibiting NF-κB activation. These findings may be used to develop a potential therapeutic drug for treating cardiac remodeling and heart failure.


PubMed | Renmin University of China, Shandong University and National Pharmaceutical Engineering Research Center
Type: Journal Article | Journal: Molecular medicine reports | Year: 2015

Hesperetin is a natural flavonoid, which has been reported to exert various biological activities and positive health effects on mammalian cells. The present study aimed to investigate the effects of hesperetin on the proliferation of primary cultured rat pulmonary artery smooth muscle cells (PASMCs), and to elucidate the possible underlying molecular mechanisms. The results of the present study indicated that hesperetin was able to inhibit the proliferation and DNA synthesis of plateletderived growth factorBB (PDGFBB)induced PASMCs in a dose and timedependent manner, without exerting cell cytotoxicity. In addition, hesperetin blocked the progression of the cell cycle from G0/G1 to S phase, which was correlated with the decreased mRNA expression levels of cyclin D1, cyclin E, cyclindependent kinase (CDK)2 and CDK4, and the increased mRNA expression levels of p27. Furthermore, the antiproliferative effects of hesperetin were associated with suppression of the AKT/glycogen synthase kinase (GSK)3 and p38 signaling pathway, but were not associated with the extracellular signalregulated kinases 1/2 and cJun Nterminal kinases signaling pathways. These results suggested that hesperetin may inhibit PDGFaBBinduced PASMC proliferation via the AKT/GSK3 signaling pathway, and that it may possess therapeutic potential for the treatment of pulmonary vascular remodeling diseases.


Deng W.,Fudan University | Li J.,Fudan University | Yao P.,Fudan University | He F.,National Pharmaceutical Engineering Research Center | Huang C.,National Pharmaceutical Engineering Research Center
Macromolecular Bioscience | Year: 2010

In this report, we developed a simple and green process of simultaneous formation of doxorubicin-BSA-dextran nanoparticles in aqueous solution and high-effective encapsulation of doxorubicin. In the presence of BSA-dextran conjugates, which were produced by Maillard reaction, a binding of doxorubicin with BSA can suppress the self-aggregation of unprotonated doxorubicin. After a heat treatment, the gelation of BSA results in a formation of the nanoparticles and the doxorubicin was fixed inside the nanoparticles. The dextran shell makes the nanoparticles dispersible in solution. The nanoparticles have a spherical morphology and a hydrodynamic radius of about 90 nm. Importantly, the nanoparticles can significantly prolong the life of murine ascites hepatoma H22 tumor-bearing mice.Binding of doxorubicin with BSA can suppress the self-aggregation of unprotonated doxorubicin. After a heat treatment, the gelation of BSA results in a formation of doxorubicin-BSA-dextran nanoparticles and the doxorubicin was loaded inside the particles effectively. The dextran conjugated to the BSA through Maillard reaction stabilizes the nanoparticles in solution. The nanoparticles can significantly prolong the life of H22 tumor-bearing mice. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Chen Z.,National Pharmaceutical Engineering Research Center | Chen Z.,Shanghai Institute of Pharmaceutical Industry | Deng J.,National Pharmaceutical Engineering Research Center | Deng J.,Shanghai Institute of Pharmaceutical Industry | And 4 more authors.
International Journal of Nanomedicine | Year: 2012

Background: Integrins αvβ3 and αvβv, both of which specifically recognize the Arg-Gly-Asp (RGD) motif, are overexpressed on many solid tumors and in tumor neovasculature. Thus, coupling the RGD motif to the liposomal surface for achieving active targeting can be a promising strategy for the treatment of tumors. Methods: Cyclo(Arg-Gly-Asp-D-Phe-Cys) (cRGD) was covalently coupled with the liposomal membrane surface, followed by coating with poly(ethylene glycol) (PEG) using the post-insertion technique. The coupling efficiency of cRGD was determined. Doxorubicin as a model anticancer drug was loaded into liposomes using an ammonium sulfate gradient method to investigate the encapsulation efficiency, cellular uptake by the integrin-overexpressing human glioma cell line U87MG in vitro, and pharmacokinetic properties in Sprague-Dawley rats. Results: cRGD was conjugated to the liposomal surface by a thiol-maleimide coupling reaction. The coupling efficiency reached 98%. The encapsulation efficiency of doxorubicin in liposomes was more than 98%. The flow cytometry test result showed that cRGD-modified liposomes (RGD-DXRL-PEG) had higher cell uptake by U87MG cells, compared with nontargeted liposomes (DXRL-PEG). The cellular uptake was significantly inhibited in the presence of excess free cRGD. Both the targeted (t1/2 = 24.10 hours) and non-targeted (t1/2 = 25.32 hours) liposomes showed long circulating properties in rat plasma. The area under the curve of the targeted and nontargeted liposomes was 6.4-fold and 8.3-fold higher than that of doxorubicin solution, respectively. Conclusion: This study indicates preferential targeting and long circulating properties for cRGD-modified liposomes in vivo, which could be used as a potential targeted liposomal drug delivery system to treat human glioma. © 2012 Chen et al, publisher and licensee Dove Medical Press Ltd.


Cheng S.,Jiangxi University of Traditional Chinese Medicine | Zhao H.,Jiangxi University of Traditional Chinese Medicine | Zuo Z.,Jiangxi University of Traditional Chinese Medicine | Wang Y.,Fuzhou University | And 2 more authors.
Zhongguo Zhongyao Zazhi | Year: 2011

Objective: To observe effect of oral scorpio and scolopendra powder on T-cell subsets in peripheral blood and intestine from rats with collagen induced arthritis (CIA). Method: 60 rats were randomly divided into 6 groups: normal control group, model control group, low-dose scorpio and scolopendra group, middle-dose scorpio and scolopendra group, high-dose scorpio and scolopendra group, and type II collagen group. Rat's rheumatoid arthritis was induced by collagen II (C II). Level of T-cell subsets from peripheral blood and intestine was measured by flow cytometry. Result: CD4 + T cellular level was obviously increased (P < 0.05 or. P < 0.01) or kept increased tendency in peripheral blood and intestine from the model group compared with that of the normal group, while the ratio of CD4 +/CD8 + in intestine was obviously descent but the contrary in peripheral blood (P < 0.05 or P < 0.01). CD4 +, CD8 + T cellular level in intestine were obviously descent and the ratio of CD4 +/CD8 + increased in all treated groups when compared with in the model group (P < 0.05 or P < 0.01). However, CD4 + T cellular level and the ratio of CD4 +/CD8 + in peripheral blood were remarkablely decreased. Conclusion: The mechanism that scorpio and scolopendra could treat rat's rheumatoid arthritis may be regulating balance of T-lymphocyte subsets in peripheral blood and intestine.


Liu W.,Jiangxi University of Traditional Chinese Medicine | Huang K.,National Pharmaceutical Engineering Research Center | Rao X.,National Pharmaceutical Engineering Research Center | Liu X.,Jiangxi University of Traditional Chinese Medicine | And 3 more authors.
Zhongguo Zhongyao Zazhi | Year: 2011

Objective: To prepare an effective and water-soluble lubricant. Method: Co-sprayed lubricant (L-leucine and polyethylene glycol 6000 co-sprayed according to a certain proportion) and mixed lubricant (the physical mixture of spayed L-leucine and crushed polyethylene glycol 6000) were prepared and polyethylene glycol 6000, L-leucine, magnesium stearate, sodium stearyl fumarate and sodium chloride are crushed and sieved, respectively. Residual force, appearance of solution and disintegration time were considered as response variables of the lubrication effect to evaluate different lubricants. The changes of the co-sprayed lubricant were studied by differential scanning calorimetry, fourier infrared, electronic scanning microscope and X-ray diffraction. Result: The efficacy of co-sprayed lubricant is better than other lubricants. Efficacy is improved by external form change without inner components and crystal changes. Conclusion: Co-sprayed lubricant is a good water soluble tablet lubricant which has good efficacy.


PubMed | National Pharmaceutical Engineering Research Center
Type: | Journal: International journal of nanomedicine | Year: 2012

Integrins (v)(3) and (v)(5), both of which specifically recognize the Arg-Gly-Asp (RGD) motif, are overexpressed on many solid tumors and in tumor neovasculature. Thus, coupling the RGD motif to the liposomal surface for achieving active targeting can be a promising strategy for the treatment of tumors.Cyclo(Arg-Gly-Asp-D-Phe-Cys) (cRGD) was covalently coupled with the liposomal membrane surface, followed by coating with poly(ethylene glycol) (PEG) using the post-insertion technique. The coupling efficiency of cRGD was determined. Doxorubicin as a model anticancer drug was loaded into liposomes using an ammonium sulfate gradient method to investigate the encapsulation efficiency, cellular uptake by the integrin-overexpressing human glioma cell line U87MG in vitro, and pharmacokinetic properties in Sprague-Dawley rats.cRGD was conjugated to the liposomal surface by a thiol-maleimide coupling reaction. The coupling efficiency reached 98%. The encapsulation efficiency of doxorubicin in liposomes was more than 98%. The flow cytometry test result showed that cRGD-modified liposomes (RGD-DXRL-PEG) had higher cell uptake by U87MG cells, compared with nontargeted liposomes (DXRL-PEG). The cellular uptake was significantly inhibited in the presence of excess free cRGD. Both the targeted (t(1/2) = 24.10 hours) and non-targeted (t(1/2) = 25.32 hours) liposomes showed long circulating properties in rat plasma. The area under the curve of the targeted and nontargeted liposomes was 6.4-fold and 8.3-fold higher than that of doxorubicin solution, respectively.This study indicates preferential targeting and long circulating properties for cRGD-modified liposomes in vivo, which could be used as a potential targeted liposomal drug delivery system to treat human glioma.

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