National Pharmaceutical Engineering Research Center

Shanghai, China

National Pharmaceutical Engineering Research Center

Shanghai, China
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Qi J.,Fudan University | Yao P.,Fudan University | He F.,National Pharmaceutical Engineering Research Center | Yu C.,National Pharmaceutical Engineering Research Center | Huang C.,National Pharmaceutical Engineering Research Center
International Journal of Pharmaceutics | Year: 2010

Biocompatible bovine serum albumin (BSA)-dextran-chitosan nanoparticles were fabricated by heating the mixture of chitosan and BSA-dextran conjugates by virtue of the electrostatic attraction between BSA and chitosan as well as the gelation of BSA. The BSA-dextran conjugates were prepared by Maillard reaction. The nanoparticles were characterized by light scattering, ζ-potential, atomic force microscopy and pyrene fluorescence. The nanoparticles having a spherical shape and hydrodynamic diameters of 130-230. nm are stable in physiological condition. Doxorubicin can be effectively loaded into the nanoparticles after changing the pH of their mixture to 7.4 by virtue of the electrostatic and hydrophobic interactions between the nanoparticles and doxorubicin. The antitumor effects of doxorubicin loaded nanoparticles were investigated by the tumor inhibition and survivability of murine ascites hepatoma H22 tumor-bearing mice. The loaded nanoparticles can largely decrease the toxicity of doxorubicin and significantly increase the survivability of the tumor-bearing mice. © 2010 Elsevier B.V.


Ning B.,China Pharmaceutical University | Ning B.,National Institutes for Food and Drug Control | Liu X.,Beijing Union Second Pharmaceutical Factory | Luan H.,National Pharmaceutical Engineering Research Center | And 5 more authors.
Journal of Pharmaceutical Innovation | Year: 2015

Purpose: In this study, a new parameter, volume under response surface (VURS), based on the multiple integrals response surface (MIRS) was applied to establish in vitro-in vivo correlations (IVIVC) refer to in vitro dissolution data and in vivo pharmacokinetic data. Materials and methods: The in vivo predictive capacity of f2 factor, dissolution efficiency (DE), and VURS were compared by investigating the multi-sourced diclofenac sodium extended-release tablets. In vitro dissolution tests were investigated under various conditions. Beagle dogs were used for in vivo pharmacokinetic study as a preliminary investigation of the new approach. In vivo pharmacokinetic experiments were conducted based on the crossed-over design principle, and the blood concentration was determined by LC-MS/MS method. Results: Data indicated both DE value and f2 factor were unable to discriminate the significant difference in relative bioavailability among the test formulations, although they could suggest in vivo bio-inequivalent risk to some extent. VURS is successfully explored to establish an IVIVC in beagle dogs with diclofenac sodium extended-release formulations with similar release mechanism. Conclusions: Compared with DE value and f2 factor, the advantage of VURS was demonstrated to predict in vivo parameters of test formulation with a similar or dissimilar release mechanism. © 2015, Springer Science+Business Media New York.


Hao H.,Fudan University | Ma Q.,National Pharmaceutical Engineering Research Center | Huang C.,National Pharmaceutical Engineering Research Center | He F.,National Pharmaceutical Engineering Research Center | Yao P.,Fudan University
International Journal of Pharmaceutics | Year: 2013

Biocompatible and biodegradable doxorubicin loaded nanoparticles with targeting ability were prepared from BSA-dextran-folic acid conjugate via a pH adjustment and heating process. The BSA-dextran-folic acid conjugate was produced by an esterification reaction between folic acid and dextran and then the Maillard reaction between the modified dextran and BSA. The nanoparticles have a size about 90 nm and excellent dispersibility at pH 7.4 aqueous solution. The doxorubicin loading efficiency and loading amount of the nanoparticles are larger than 90% and 14%, respectively. The antitumor activity and toxicity of the nanoparticles were evaluated through murine ascites hepatoma H22 tumor-bearing mice. The nanoparticles allow the administration of the doxorubicin with higher dose. At doxorubicin dose of 10 mg/kg, the nanoparticles can achieve 88.9% of the tumor inhibition rate that is the same as the free doxorubicin at the dose of 5 mg/kg. Importantly, the nanoparticles can decrease the toxicity of doxorubicin that results in a significant increase of the average life time in comparison with the free doxorubicin as well as the nanoparticles without folic acid. © 2013 Elsevier B.V. All rights reserved.


Xiao L.,National Pharmaceutical Engineering Research Center | Chen Q.,National Pharmaceutical Engineering Research Center | Bao Y.,National Pharmaceutical Engineering Research Center | Pan F.,National Pharmaceutical Engineering Research Center
Asian Journal of Pharmaceutical Sciences | Year: 2010

Purpose: The aim of this paper was to develop a novel polymer-alloys technique for preparing controlled release microspheres of nomegestrol by using PLGA and PLCG, two kinds of polyester, as the combined matrix. Methods: Both in vitro and in vivo release characteristics of the obtained microspheres were demonstrated and the factors influencing the drug release pattern were discussed. In addition, the mechanism of the drug release was also investigated. Results: The results showed that nomegestrol released from the microspheres in a well-controlled pattern: low burst release on 1st day, shortened/eliminated lag time and drug released in a zero-order profile for 30 d. Conclusion: This method successfully overcame the drawbacks of traditional microencapsulation method in which the single kind of polyester was used as the matrix and uneven drug release profile was obtained.


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.


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.


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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