The antithrombotic and antiplatelet effects of two fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica were compared in order to examine the influence of chemical charact...The antithrombotic and antiplatelet effects of two fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica were compared in order to examine the influence of chemical character on their antithrombotic activity and the possible mechanism. Both LMW fucoidan fractions exhibited favorable antithrombotic activity in an Fecl3-induced arterial thrombosis. The antithrombotic activity of LMW fucoidan was related with decrease of TXB2 and whole blood viscosity and hematocrit. LMW fucoidan showed a correlation between anticoagulant, antiaggregant and antithrombotic effects in vivo. For LMW fucoidan, antithrombotic activity required high dose of 5-10 nmol kg-1, concomitantly with increase in anticoagulant activity and inhibition of platelet aggregation. Administration of LMW fucoidan significantly promoted the 6-keto-PGF1α content and decreased the TXB2 content, indicating its inhibition of tissue factor pathway and regulation of metabolism of arachidonic acid. By comparison, highly sulfated fucoidan LF2 with Mw 3900 seemed to be a more suitable choice for antithrombotic drug for its antithrombotic activity accompanied with specific inhibitory activity on platelet aggregation, low anticoagulant activity and low hemorrhagic risk in vivo.展开更多
We adopted the response surface methodology using single factor and orthogonal experiments to optimize four types of antimicrobial agents that could inhibit biofilm formation by Streptococcus mutans, which is commonly...We adopted the response surface methodology using single factor and orthogonal experiments to optimize four types of antimicrobial agents that could inhibit biofilm formation by Streptococcus mutans, which is commonly found in the human oral cavity and causes tooth decay. The objective was to improve the function of marine Arthrobacter oxydans KQll dextranase mouthwash (designed and developed by our laboratory). The experiment was conducted in a three-level, four-variable central composite design to determine the best combination of ZnSO4, lysozyme, citric acid and chitosan. The optimized antibacterial agents were 2.16 g/L ZnSO4, 14 g/L lysozyme, 4.5 g/L citric acid and 5 g/L chitosan. The biofilm formation inhibition reached 84.49%. In addition, microscopic observation of the biofilm was performed using scanning electron microscopy and confocal laser scanning microscopy. The optimized formula was tested in marine dextranase Arthrobacter oxydans KQ11 mouthwash and enhanced the inhibition of S. mutans. This work may be promoted for the design and development of future marine dextranase oral care products.展开更多
After entering 2010, as main varieties patents of the global non-peptide angiotensin II receptor antagonists (ARB) expire, strong growth of anti-hypertensive drug market will tend to slow down. In drugs acting on th...After entering 2010, as main varieties patents of the global non-peptide angiotensin II receptor antagonists (ARB) expire, strong growth of anti-hypertensive drug market will tend to slow down. In drugs acting on the cardiovascular and blood system, antithrombotie drugs will become a new attraction on the market. Antithrombotic drugs are primarily formed by the anti-platelet aggregation, coagulation system activation of plasminogen thrombolytic drugs and the like. Antiplatelet drugs have both prevention and treatment effect, are the main category of antithrombotic drugs. According to IMS Health data, in 2008, sale of anti-thrombosis drug in global market is 180 million U.S. dollars, an increase of 16 %, while in 2009 the growth rate is only 7.95%, reaching $ 19.5 billion, growth rate of antithrombotic drugs is 7.13% in the world' s major pharmaceutical market.展开更多
Multi-functional mikto-arm star polymers containing three different arms [hydrophilic, SN-38-P(OEGMAs_9)11, cationizable, SN-38-P(DMAEMA)3s and hydrophobic, SN-38-P(BMA)26] were prepared by RAFT polymerization v...Multi-functional mikto-arm star polymers containing three different arms [hydrophilic, SN-38-P(OEGMAs_9)11, cationizable, SN-38-P(DMAEMA)3s and hydrophobic, SN-38-P(BMA)26] were prepared by RAFT polymerization via an arm-first approach using a cleavable cross-linker. The star polymers were cleaved to the linear arms with tributylphosphine as a reducing agent. The decrease in molecular weight observed is consistent with the initial stars having approximately five arms, Blue fluorescence was observed when a solution of mikto-arm star was irradiated under a 365 nm light proving the retention of the SN-38 moiety during star formation by RAFT polymerization. Thus these polymer-drug conjugates can be considered as potential delivery vehicles for cancer therapy. The P(DMAEMA) arms can be quaternized using iodomethane, allowing star polymers to bind negatively charged small interfering RNA (siRNA) and potentially be used as a carrier for that material.展开更多
Poly(caprolactone-b-2-vinylpyridine) (PCL-P2VP) coated with folate-conjugated M13 (FA-M13) provides a nanosized delivery system which is capable of encapsulating hydrophobic antitumor drugs such as doxorubicin ...Poly(caprolactone-b-2-vinylpyridine) (PCL-P2VP) coated with folate-conjugated M13 (FA-M13) provides a nanosized delivery system which is capable of encapsulating hydrophobic antitumor drugs such as doxorubicin (DOX). The DOXqoaded FA-M13-PCL-P2VP assemblies had an average diameter of approximately 200 nm and their structure was characterized using transmission electron microscopy, scanning electron microscopy, and dynamic light scattering. The particles were stable at physiological pH but could be degraded at a lower pH. The release of DOX from the nanoassemblies under acidic conditions was shown to be significantly faster than that observed at physiological pH. In addition, the DOX-loaded FA-M13-PCL-P2VP particles showed a distinctly greater cellular uptake and cytotoxicity against folate-receptor-positive cancer cells than folate-receptor-negative cells, indicating that the receptor facilitates folate uptake via receptor-mediated endocytosis. Furthermore, the DOX-loaded particles also had a significantly higher tumor uptake and selectivity compared to free DOX. This study therefore offers a new way to fabricate nanosized drug delivery vehicles.展开更多
At the intersection between treatment and diagnosis, nanoparticles technologies are strongly impacting the development of both therapeutic and diagnostic agents.Consequently, the development of novel modalities for co...At the intersection between treatment and diagnosis, nanoparticles technologies are strongly impacting the development of both therapeutic and diagnostic agents.Consequently, the development of novel modalities for concomitant noninvasive therapy and diagnostics known as theranostics as a single platform has gained significant interests. These multifunctional theranostic platforms include carbon-based nanomaterials(e.g., carbon nanotubes), drug conjugates, aliphatic polymers, micelles, vesicles, core-shell nanoparticles, microbubbles and dendrimers bearing different contrast agents and drugs, such as cytotoxic compounds in the oncology domain. Dendrimers emerged as a new class of highly tunable hyperbranched polymers, and have been developed as useful theranostic platforms. Magnetic resonance imaging, gamma scintigraphy, computed tomography and optical imaging are the main techniques developed with dendrimers in the theranostic domain in oncology. Different imaging agents have been used such as Gd(Ⅲ),19F, Fe2O3(MRI),76Br(PET),111In,88Y,153Gd,188Re,131I(SPECT),177Lu,gold(CT) and boronated groups, siliconnaphthalocyanines,dialkylcarbocyanines and QDs(optical imaging dyes).展开更多
基金supported in part by the Notional Natural Science Foundation of China (No.30800858)the Shandong Natural Science Foundation (No.ZR2010 CQ020)
文摘The antithrombotic and antiplatelet effects of two fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica were compared in order to examine the influence of chemical character on their antithrombotic activity and the possible mechanism. Both LMW fucoidan fractions exhibited favorable antithrombotic activity in an Fecl3-induced arterial thrombosis. The antithrombotic activity of LMW fucoidan was related with decrease of TXB2 and whole blood viscosity and hematocrit. LMW fucoidan showed a correlation between anticoagulant, antiaggregant and antithrombotic effects in vivo. For LMW fucoidan, antithrombotic activity required high dose of 5-10 nmol kg-1, concomitantly with increase in anticoagulant activity and inhibition of platelet aggregation. Administration of LMW fucoidan significantly promoted the 6-keto-PGF1α content and decreased the TXB2 content, indicating its inhibition of tissue factor pathway and regulation of metabolism of arachidonic acid. By comparison, highly sulfated fucoidan LF2 with Mw 3900 seemed to be a more suitable choice for antithrombotic drug for its antithrombotic activity accompanied with specific inhibitory activity on platelet aggregation, low anticoagulant activity and low hemorrhagic risk in vivo.
基金Supported by the National Natural Science Foundation of China(Nos.3147171931271929)+2 种基金the Jiangsu Province and Technology Support Program(No.BE2013662)the Lianyungang Fifth“521 High-Level Talent Training Project”the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘We adopted the response surface methodology using single factor and orthogonal experiments to optimize four types of antimicrobial agents that could inhibit biofilm formation by Streptococcus mutans, which is commonly found in the human oral cavity and causes tooth decay. The objective was to improve the function of marine Arthrobacter oxydans KQll dextranase mouthwash (designed and developed by our laboratory). The experiment was conducted in a three-level, four-variable central composite design to determine the best combination of ZnSO4, lysozyme, citric acid and chitosan. The optimized antibacterial agents were 2.16 g/L ZnSO4, 14 g/L lysozyme, 4.5 g/L citric acid and 5 g/L chitosan. The biofilm formation inhibition reached 84.49%. In addition, microscopic observation of the biofilm was performed using scanning electron microscopy and confocal laser scanning microscopy. The optimized formula was tested in marine dextranase Arthrobacter oxydans KQ11 mouthwash and enhanced the inhibition of S. mutans. This work may be promoted for the design and development of future marine dextranase oral care products.
文摘After entering 2010, as main varieties patents of the global non-peptide angiotensin II receptor antagonists (ARB) expire, strong growth of anti-hypertensive drug market will tend to slow down. In drugs acting on the cardiovascular and blood system, antithrombotie drugs will become a new attraction on the market. Antithrombotic drugs are primarily formed by the anti-platelet aggregation, coagulation system activation of plasminogen thrombolytic drugs and the like. Antiplatelet drugs have both prevention and treatment effect, are the main category of antithrombotic drugs. According to IMS Health data, in 2008, sale of anti-thrombosis drug in global market is 180 million U.S. dollars, an increase of 16 %, while in 2009 the growth rate is only 7.95%, reaching $ 19.5 billion, growth rate of antithrombotic drugs is 7.13% in the world' s major pharmaceutical market.
基金the China Scholarship Council for partial financial support
文摘Multi-functional mikto-arm star polymers containing three different arms [hydrophilic, SN-38-P(OEGMAs_9)11, cationizable, SN-38-P(DMAEMA)3s and hydrophobic, SN-38-P(BMA)26] were prepared by RAFT polymerization via an arm-first approach using a cleavable cross-linker. The star polymers were cleaved to the linear arms with tributylphosphine as a reducing agent. The decrease in molecular weight observed is consistent with the initial stars having approximately five arms, Blue fluorescence was observed when a solution of mikto-arm star was irradiated under a 365 nm light proving the retention of the SN-38 moiety during star formation by RAFT polymerization. Thus these polymer-drug conjugates can be considered as potential delivery vehicles for cancer therapy. The P(DMAEMA) arms can be quaternized using iodomethane, allowing star polymers to bind negatively charged small interfering RNA (siRNA) and potentially be used as a carrier for that material.
基金We are grateful for financial support from the US National Science Foundation (NSF) (CAREER program and No. DMR-0706431), US Department of Defense (DoD) (No. W911NF-09-1-0236), the Alfred P. Sloan Scholarship, the Camille Dreyfus Teacher-Scholar Award, DoD-Army Research Office (ARO), and the W. M. Keck Foundation. We are also indebted to Dr. Udai Singh for assistance with flow cytometry and Laying Wu for TEM and SEM analyses.
文摘Poly(caprolactone-b-2-vinylpyridine) (PCL-P2VP) coated with folate-conjugated M13 (FA-M13) provides a nanosized delivery system which is capable of encapsulating hydrophobic antitumor drugs such as doxorubicin (DOX). The DOXqoaded FA-M13-PCL-P2VP assemblies had an average diameter of approximately 200 nm and their structure was characterized using transmission electron microscopy, scanning electron microscopy, and dynamic light scattering. The particles were stable at physiological pH but could be degraded at a lower pH. The release of DOX from the nanoassemblies under acidic conditions was shown to be significantly faster than that observed at physiological pH. In addition, the DOX-loaded FA-M13-PCL-P2VP particles showed a distinctly greater cellular uptake and cytotoxicity against folate-receptor-positive cancer cells than folate-receptor-negative cells, indicating that the receptor facilitates folate uptake via receptor-mediated endocytosis. Furthermore, the DOX-loaded particles also had a significantly higher tumor uptake and selectivity compared to free DOX. This study therefore offers a new way to fabricate nanosized drug delivery vehicles.
基金support of FCT-Fundacao para a Ciência e a Tecnologia(project PEst-OE/QUI/UI0674/2013,CQM,Portuguese Government funds)ARDITI through the project M1420-01-0145-FEDER-000005-Centro de Química da Madeira-CQM+(Madeira 14-20)+2 种基金the funds from Centre National de la Recherche Scientifique(CNRS,France)the support by the National Natural Science Foundation of China(21773026 and 81761148028)the Sino-French Caiyuanpei Programme
文摘At the intersection between treatment and diagnosis, nanoparticles technologies are strongly impacting the development of both therapeutic and diagnostic agents.Consequently, the development of novel modalities for concomitant noninvasive therapy and diagnostics known as theranostics as a single platform has gained significant interests. These multifunctional theranostic platforms include carbon-based nanomaterials(e.g., carbon nanotubes), drug conjugates, aliphatic polymers, micelles, vesicles, core-shell nanoparticles, microbubbles and dendrimers bearing different contrast agents and drugs, such as cytotoxic compounds in the oncology domain. Dendrimers emerged as a new class of highly tunable hyperbranched polymers, and have been developed as useful theranostic platforms. Magnetic resonance imaging, gamma scintigraphy, computed tomography and optical imaging are the main techniques developed with dendrimers in the theranostic domain in oncology. Different imaging agents have been used such as Gd(Ⅲ),19F, Fe2O3(MRI),76Br(PET),111In,88Y,153Gd,188Re,131I(SPECT),177Lu,gold(CT) and boronated groups, siliconnaphthalocyanines,dialkylcarbocyanines and QDs(optical imaging dyes).