<?xml version="1.0" encoding="UTF-8" ?><xml><records><record><database name="Alex2014.enl" path="\\ad.nfit.au.dk\NFDFS\Users\riber\Documents\Webpage\literature\Alex2014.enl">Alex2014.enl</database><source-app name="EndNote" version="16.0">EndNote</source-app><rec-number>23</rec-number><foreign-keys><key app="EN" db-id="0wtxswe0cwwvd8esx9pps2wf2rxxst90w9zs">23</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Wohl, Benjamin M.</style></author><author><style face="normal" font="default" size="100%">Smith, Anton A. A.</style></author><author><style face="normal" font="default" size="100%">Jensen, Bettina E. B.</style></author><author><style face="normal" font="default" size="100%">Zelikin, Alexander N.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Macromolecular (pro)drugs with concurrent direct activity against the hepatitis C virus and inflammation</style></title><secondary-title><style face="normal" font="default" size="100%">Journal of Controlled Release</style></secondary-title></titles><periodical><full-title><style face="normal" font="default" size="100%">Journal of Controlled Release</style></full-title></periodical><pages><style face="normal" font="default" size="100%">197-207</style></pages><volume><style face="normal" font="default" size="100%">196</style></volume><number><style face="normal" font="default" size="100%">0</style></number><keywords><keyword><style face="normal" font="default" size="100%">Macromolecular prodrugs</style></keyword><keyword><style face="normal" font="default" size="100%">Polymer therapeutics</style></keyword><keyword><style face="normal" font="default" size="100%">Ribavirin</style></keyword><keyword><style face="normal" font="default" size="100%">Antiviral</style></keyword><keyword><style face="normal" font="default" size="100%">Drug delivery</style></keyword><keyword><style face="normal" font="default" size="100%">Hepatitis C</style></keyword></keywords><dates><year><style face="normal" font="default" size="100%">2014</style></year><pub-dates><date><style face="normal" font="default" size="100%">30</style></date></pub-dates></dates><isbn><style face="normal" font="default" size="100%">0168-3659</style></isbn><abstract><style face="normal" font="default" size="100%">Macromolecular prodrugs (MPs) are a powerful tool to alleviate side-effects and improve the efficacy of the broad-spectrum antiviral agent ribavirin. In this work, we sought an understanding of what makes an optimal formulation within the macromolecular parameter space — nature of the polymer carrier, average molar mass, drug loading, or a good combination thereof. A panel of MPs based on biocompatible synthetic vinylic and (meth)acrylic polymers was tested in an anti-inflammatory assay with relevance to alleviating inflammation in the liver during hepatitis C infection. Pristine polymer carriers proved to have a pronounced anti-inflammatory activity, a notion which may prove significant in developing MPs for antiviral and anticancer treatments. With conjugated ribavirin, MPs revealed enhanced activity but also higher toxicity. Therapeutic windows and therapeutic indices were determined and discussed to reveal the most potent formulation and those with optimized safety. Polymers were also tested as inhibitors of replication of the hepatitis C viral RNA using a subgenomic viral replicon system. For the first time, negatively charged polymers are revealed to have an intracellular activity against hepatitis C virus replication. Concerted activity of the polymer and ribavirin afforded MPs which significantly increased the therapeutic index of ribavirin-based treatment. Taken together, the systematic investigation of the macromolecular space identified lead candidates with high efficacy and concurrent direct activity against the hepatitis C virus and inflammation.</style></abstract><urls><related-urls><url><style face="normal" font="default" size="100%">http://www.sciencedirect.com/science/article/pii/S0168365914006816</style></url></related-urls><pdf-urls><url>internal-pdf://Macromolecular-(pro)drugs-with-concurrent-direct-act-2792661504/Macromolecular-(pro)drugs-with-concurrent-direct-activity-against-the-hepatitis-C-virus-and-inflammation_small.png</url></pdf-urls></urls><electronic-resource-num><style face="normal" font="default" size="100%">10.1016/j.jconrel.2014.09.032</style></electronic-resource-num></record><record><database name="Alex2014.enl" path="\\ad.nfit.au.dk\NFDFS\Users\riber\Documents\Webpage\literature\Alex2014.enl">Alex2014.enl</database><source-app name="EndNote" version="16.0">EndNote</source-app><rec-number>24</rec-number><foreign-keys><key app="EN" db-id="0wtxswe0cwwvd8esx9pps2wf2rxxst90w9zs">24</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Kock, Anders</style></author><author><style face="normal" font="default" size="100%">Zuwala, Kaja</style></author><author><style face="normal" font="default" size="100%">Smith, Anton A. A.</style></author><author><style face="normal" font="default" size="100%">Ruiz-Sanchis, Pau</style></author><author><style face="normal" font="default" size="100%">Wohl, Benjamin M.</style></author><author><style face="normal" font="default" size="100%">Tolstrup, Martin</style></author><author><style face="normal" font="default" size="100%">Zelikin, Alexander N.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Disulfide reshuffling triggers the release of a thiol-free anti-HIV agent to make up fast-acting, potent macromolecular prodrugs</style></title><secondary-title><style face="normal" font="default" size="100%">Chemical Communications</style></secondary-title></titles><periodical><full-title><style face="normal" font="default" size="100%">Chemical Communications</style></full-title></periodical><pages><style face="normal" font="default" size="100%">14498-14500</style></pages><volume><style face="normal" font="default" size="100%">50</style></volume><number><style face="normal" font="default" size="100%">93</style></number><dates><year><style face="normal" font="default" size="100%">2014</style></year><pub-dates><date><style face="normal" font="default" size="100%">29</style></date></pub-dates></dates><publisher><style face="normal" font="default" size="100%">The Royal Society of Chemistry</style></publisher><isbn><style face="normal" font="default" size="100%">1359-7345</style></isbn><abstract><style face="normal" font="default" size="100%">The release of azidothymidine from macromolecular prodrugs was designed to respond to the intracellular disulfide reshuffling. This drug has no thiol groups, and a response to this trigger was engineered using a self-immolative linker. The resulting formulations were fast-acting, efficacious, and highly potent with regards to suppressing the infectivity of the virus.</style></abstract><work-type><style face="normal" font="default" size="100%">10.1039/C4CC04280H</style></work-type><urls><related-urls><url><style face="normal" font="default" size="100%">http://dx.doi.org/10.1039/C4CC04280H</style></url></related-urls><pdf-urls><url>internal-pdf://AZT-SIL-small-1483827712/AZT-SIL-small.png</url></pdf-urls></urls><electronic-resource-num><style face="normal" font="default" size="100%">10.1039/C4CC04280H</style></electronic-resource-num></record><record><database name="Alex2014.enl" path="\\ad.nfit.au.dk\NFDFS\Users\riber\Documents\Webpage\literature\Alex2014.enl">Alex2014.enl</database><source-app name="EndNote" version="16.0">EndNote</source-app><rec-number>25</rec-number><foreign-keys><key app="EN" db-id="0wtxswe0cwwvd8esx9pps2wf2rxxst90w9zs">25</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Smith, Anton A. A.</style></author><author><style face="normal" font="default" size="100%">Kryger, Mille B. L.</style></author><author><style face="normal" font="default" size="100%">Wohl, Benjamin M.</style></author><author><style face="normal" font="default" size="100%">Ruiz-Sanchis, Pau</style></author><author><style face="normal" font="default" size="100%">Zuwala, Kaja</style></author><author><style face="normal" font="default" size="100%">Tolstrup, Martin</style></author><author><style face="normal" font="default" size="100%">Zelikin, Alexander N.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Macromolecular (pro)drugs in antiviral research</style></title><secondary-title><style face="normal" font="default" size="100%">Polymer Chemistry</style></secondary-title></titles><periodical><full-title><style face="normal" font="default" size="100%">Polymer Chemistry</style></full-title></periodical><pages><style face="normal" font="default" size="100%">6407-6425</style></pages><volume><style face="normal" font="default" size="100%">5</style></volume><number><style face="normal" font="default" size="100%">22</style></number><dates><year><style face="normal" font="default" size="100%">2014</style></year><pub-dates><date><style face="normal" font="default" size="100%">26</style></date></pub-dates></dates><publisher><style face="normal" font="default" size="100%">The Royal Society of Chemistry</style></publisher><isbn><style face="normal" font="default" size="100%">1759-9954</style></isbn><abstract><style face="normal" font="default" size="100%">Macromolecular (pro)drugs are a sub-discipline of medicinal and polymer chemistries aiming to optimize the delivery of drugs to their site of action. In recent decades, this field of science has undergone a tremendous development, with the soundest achievements registered in the delivery of anticancer drugs. Surprisingly, the development of these tools for applications in antiviral treatment lags significantly behind - despite the fact that the first in vivo successes of polymers in fighting viruses were reported half a century ago. Furthermore, the unique scope and utility of polymers in antiviral research is that macromolecules themselves exhibit highly potent activity against diverse viruses. Herein, in an attempt to revive the research interest in this field, we aim to provide an overview of successes (and failures) of polymers as antiviral agents and macromolecular prodrugs. Specifically, we discuss inhibition of the entry of the virus into mammalian cells by polymers, give an overview of the synthetic schemes applied for the conjugation of drugs to carrier polymers, and also present guidance with regard to potential reporter systems which can be used for the characterization of novel drug delivery systems in virus-free cell cultures.</style></abstract><work-type><style face="normal" font="default" size="100%">10.1039/C4PY00624K</style></work-type><urls><related-urls><url><style face="normal" font="default" size="100%">http://dx.doi.org/10.1039/C4PY00624K</style></url></related-urls><pdf-urls><url>internal-pdf://antiviral-macromolecular-prodrugs-small-3060886016/antiviral-macromolecular-prodrugs-small.png</url></pdf-urls></urls><electronic-resource-num><style face="normal" font="default" size="100%">10.1039/C4PY00624K</style></electronic-resource-num></record><record><database name="Alex2014.enl" path="\\ad.nfit.au.dk\NFDFS\Users\riber\Documents\Webpage\literature\Alex2014.enl">Alex2014.enl</database><source-app name="EndNote" version="16.0">EndNote</source-app><rec-number>26</rec-number><foreign-keys><key app="EN" db-id="0wtxswe0cwwvd8esx9pps2wf2rxxst90w9zs">26</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Mendes, Ana C.</style></author><author><style face="normal" font="default" size="100%">Zelikin, Alexander N.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Enzyme Prodrug Therapy Engineered into Biomaterials</style></title><secondary-title><style face="normal" font="default" size="100%">Advanced Functional Materials</style></secondary-title></titles><periodical><full-title><style face="normal" font="default" size="100%">Advanced Functional Materials</style></full-title></periodical><pages><style face="normal" font="default" size="100%">5202-5210</style></pages><volume><style face="normal" font="default" size="100%">24</style></volume><number><style face="normal" font="default" size="100%">33</style></number><keywords><keyword><style face="normal" font="default" size="100%">enzymes</style></keyword><keyword><style face="normal" font="default" size="100%">prodrug therapy</style></keyword><keyword><style face="normal" font="default" size="100%">enzyme prodrug therapies</style></keyword><keyword><style face="normal" font="default" size="100%">drug delivery</style></keyword><keyword><style face="normal" font="default" size="100%">biomaterials</style></keyword><keyword><style face="normal" font="default" size="100%">hydrogels</style></keyword></keywords><dates><year><style face="normal" font="default" size="100%">2014</style></year><pub-dates><date><style face="normal" font="default" size="100%">25</style></date></pub-dates></dates><isbn><style face="normal" font="default" size="100%">1616-3028</style></isbn><urls><related-urls><url><style face="normal" font="default" size="100%">http://dx.doi.org/10.1002/adfm.201304312</style></url></related-urls><pdf-urls><url>internal-pdf://enzyme-prodrug-therapy-biomaterials-small-1232269312/enzyme-prodrug-therapy-biomaterials-small.png</url></pdf-urls></urls><electronic-resource-num><style face="normal" font="default" size="100%">10.1002/adfm.201304312</style></electronic-resource-num></record><record><database name="Alex2014.enl" path="\\ad.nfit.au.dk\NFDFS\Users\riber\Documents\Webpage\literature\Alex2014.enl">Alex2014.enl</database><source-app name="EndNote" version="16.0">EndNote</source-app><rec-number>27</rec-number><foreign-keys><key app="EN" db-id="0wtxswe0cwwvd8esx9pps2wf2rxxst90w9zs">27</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Rasmussen, Kasper F.</style></author><author><style face="normal" font="default" size="100%">Smith, Anton A. A.</style></author><author><style face="normal" font="default" size="100%">Ruiz-Sanchis, Pau</style></author><author><style face="normal" font="default" size="100%">Edlund, Katrine</style></author><author><style face="normal" font="default" size="100%">Zelikin, Alexander N.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Cholesterol Modification of (Bio)Polymers Using UV-Vis Traceable Chemistry in Aqueous Solutions</style></title><secondary-title><style face="normal" font="default" size="100%">Macromolecular Bioscience</style></secondary-title></titles><periodical><full-title><style face="normal" font="default" size="100%">Macromolecular Bioscience</style></full-title></periodical><pages><style face="normal" font="default" size="100%">33-44</style></pages><volume><style face="normal" font="default" size="100%">14</style></volume><number><style face="normal" font="default" size="100%">1</style></number><keywords><keyword><style face="normal" font="default" size="100%">biomaterials</style></keyword><keyword><style face="normal" font="default" size="100%">cholesterol</style></keyword><keyword><style face="normal" font="default" size="100%">hydrogels</style></keyword><keyword><style face="normal" font="default" size="100%">reversible addition fragmentation chain transfer (RAFT)</style></keyword></keywords><dates><year><style face="normal" font="default" size="100%">2014</style></year><pub-dates><date><style face="normal" font="default" size="100%">23</style></date></pub-dates></dates><isbn><style face="normal" font="default" size="100%">1616-5195</style></isbn><urls><related-urls><url><style face="normal" font="default" size="100%">http://dx.doi.org/10.1002/mabi.201300286</style></url></related-urls><pdf-urls><url>internal-pdf://choloesterol-modification-of-biopolymers-small-3497282304/choloesterol-modification-of-biopolymers-small.png</url></pdf-urls></urls><electronic-resource-num><style face="normal" font="default" size="100%">10.1002/mabi.201300286</style></electronic-resource-num></record><record><database name="Alex2014.enl" path="\\ad.nfit.au.dk\NFDFS\Users\riber\Documents\Webpage\literature\Alex2014.enl">Alex2014.enl</database><source-app name="EndNote" version="16.0">EndNote</source-app><rec-number>28</rec-number><foreign-keys><key app="EN" db-id="0wtxswe0cwwvd8esx9pps2wf2rxxst90w9zs">28</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Andreasen, Sidsel O.</style></author><author><style face="normal" font="default" size="100%">Fejerskov, Betina</style></author><author><style face="normal" font="default" size="100%">Zelikin, Alexander N.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Biocatalytic polymer thin films: optimization of the multilayered architecture towards in situ synthesis of anti-proliferative drugs</style></title><secondary-title><style face="normal" font="default" size="100%">Nanoscale</style></secondary-title></titles><periodical><full-title><style face="normal" font="default" size="100%">Nanoscale</style></full-title></periodical><pages><style face="normal" font="default" size="100%">4131-4140</style></pages><volume><style face="normal" font="default" size="100%">6</style></volume><number><style face="normal" font="default" size="100%">8</style></number><dates><year><style face="normal" font="default" size="100%">2014</style></year><pub-dates><date><style face="normal" font="default" size="100%">23</style></date></pub-dates></dates><publisher><style face="normal" font="default" size="100%">The Royal Society of Chemistry</style></publisher><isbn><style face="normal" font="default" size="100%">2040-3364</style></isbn><abstract><style face="normal" font="default" size="100%">We report on the assembly of multi-layered polyelectrolyte thin films containing an immobilized enzyme to perform conversion of externally administered prodrugs and achieve delivery of the resulting therapeutics to adhering cells. Towards this goal, multi-layered coatings were assembled using poly(sodium styrene sulfonate) and poly(allylamine hydrochloride). Activity of the incorporated enzyme was quantified as a function of the assembly conditions, position of the enzyme within the multi-layered architecture, concentration of the enzyme in the adsorption solution, and concentration of the administered prodrug. Biocatalytic coatings exhibited sustained levels of enzymatic activity over at least one week of incubation in physiological buffers without signs of loss of activity of the enzyme. Developed enzyme-containing polymer films afforded zero-order release of the in situ synthesized cargo with kinetics of synthesis (nM per hour) covering at least 3 orders of magnitude. Internalization of the synthesized product by adhering cells was visualized using a fluorogenic enzyme substrate. Therapeutic utility of biocatalytic coatings was demonstrated using a myoblast cell line and a prodrug for the anti-proliferative agent, 5-fluorouridine. Taken together, this work presents a novel approach to delivery of small molecule drugs using multi-layered polymer thin films with utility in surface-mediated drug delivery, assembly of therapeutic implantable devices, and tissue engineering.</style></abstract><work-type><style face="normal" font="default" size="100%">10.1039/C3NR05999E</style></work-type><urls><related-urls><url><style face="normal" font="default" size="100%">http://dx.doi.org/10.1039/C3NR05999E</style></url></related-urls><pdf-urls><url>internal-pdf://biocatalytic-suface-coatings-2-small-1114729216/biocatalytic-suface-coatings-2-small.png</url></pdf-urls></urls><electronic-resource-num><style face="normal" font="default" size="100%">10.1039/C3NR05999E</style></electronic-resource-num></record><record><database name="Alex2014.enl" path="\\ad.nfit.au.dk\NFDFS\Users\riber\Documents\Webpage\literature\Alex2014.enl">Alex2014.enl</database><source-app name="EndNote" version="16.0">EndNote</source-app><rec-number>33</rec-number><foreign-keys><key app="EN" db-id="0wtxswe0cwwvd8esx9pps2wf2rxxst90w9zs">33</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Smith, Anton A. A.</style></author><author><style face="normal" font="default" size="100%">Wohl, Benjamin M.</style></author><author><style face="normal" font="default" size="100%">Kryger, Mille B. L.</style></author><author><style face="normal" font="default" size="100%">Hedemann, Natasha</style></author><author><style face="normal" font="default" size="100%">Guerrero-Sanchez, Carlos</style></author><author><style face="normal" font="default" size="100%">Postma, Almar</style></author><author><style face="normal" font="default" size="100%">Zelikin, Alexander N.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Macromolecular Prodrugs of Ribavirin: Concerted Efforts of the Carrier and the Drug</style></title><secondary-title><style face="normal" font="default" size="100%">Advanced Healthcare Materials</style></secondary-title></titles><periodical><full-title><style face="normal" font="default" size="100%">Advanced Healthcare Materials</style></full-title></periodical><pages><style face="normal" font="default" size="100%">1404-1407</style></pages><volume><style face="normal" font="default" size="100%">3</style></volume><number><style face="normal" font="default" size="100%">9</style></number><keywords><keyword><style face="normal" font="default" size="100%">polymers</style></keyword><keyword><style face="normal" font="default" size="100%">prodrugs</style></keyword><keyword><style face="normal" font="default" size="100%">drug delivery</style></keyword><keyword><style face="normal" font="default" size="100%">high throughput screening</style></keyword><keyword><style face="normal" font="default" size="100%">inflammation</style></keyword></keywords><dates><year><style face="normal" font="default" size="100%">2014</style></year><pub-dates><date><style face="normal" font="default" size="100%">22</style></date></pub-dates></dates><isbn><style face="normal" font="default" size="100%">2192-2659</style></isbn><urls><related-urls><url><style face="normal" font="default" size="100%">http://dx.doi.org/10.1002/adhm.201300637</style></url></related-urls><pdf-urls><url>internal-pdf://macromolecular-prodrugs-concerted-effort-small-0986692864/macromolecular-prodrugs-concerted-effort-small.png</url></pdf-urls></urls><electronic-resource-num><style face="normal" font="default" size="100%">10.1002/adhm.201300637</style></electronic-resource-num></record><record><database name="Alex2014.enl" path="\\ad.nfit.au.dk\NFDFS\Users\riber\Documents\Webpage\literature\Alex2014.enl">Alex2014.enl</database><source-app name="EndNote" version="16.0">EndNote</source-app><rec-number>30</rec-number><foreign-keys><key app="EN" db-id="0wtxswe0cwwvd8esx9pps2wf2rxxst90w9zs">30</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Fejerskov, Betina</style></author><author><style face="normal" font="default" size="100%">Jensen, Najah B. S.</style></author><author><style face="normal" font="default" size="100%">Teo, Boon M.</style></author><author><style face="normal" font="default" size="100%">Städler, Brigitte</style></author><author><style face="normal" font="default" size="100%">Zelikin, Alexander N.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Biocatalytic Polymer Coatings: On-Demand Drug Synthesis and Localized Therapeutic Effect under Dynamic Cell Culture Conditions</style></title><secondary-title><style face="normal" font="default" size="100%">Small</style></secondary-title></titles><periodical><full-title><style face="normal" font="default" size="100%">Small</style></full-title></periodical><pages><style face="normal" font="default" size="100%">1314-1324</style></pages><volume><style face="normal" font="default" size="100%">10</style></volume><number><style face="normal" font="default" size="100%">7</style></number><keywords><keyword><style face="normal" font="default" size="100%">Enzyme - prodrug therapy</style></keyword><keyword><style face="normal" font="default" size="100%">Biomaterials</style></keyword><keyword><style face="normal" font="default" size="100%">Surface mediated drug delivery</style></keyword><keyword><style face="normal" font="default" size="100%">Shear stress</style></keyword><keyword><style face="normal" font="default" size="100%">Multilayered polymer coatings</style></keyword></keywords><dates><year><style face="normal" font="default" size="100%">2014</style></year><pub-dates><date><style face="normal" font="default" size="100%">21</style></date></pub-dates></dates><isbn><style face="normal" font="default" size="100%">1613-6829</style></isbn><urls><related-urls><url><style face="normal" font="default" size="100%">http://dx.doi.org/10.1002/smll.201303101</style></url></related-urls><pdf-urls><url>internal-pdf://biocatalytic-suface-coatings-small-3731974912/biocatalytic-suface-coatings-small.png</url></pdf-urls></urls><electronic-resource-num><style face="normal" font="default" size="100%">10.1002/smll.201303101</style></electronic-resource-num></record><record><database name="Alex2014.enl" path="\\ad.nfit.au.dk\NFDFS\Users\riber\Documents\Webpage\literature\Alex2014.enl">Alex2014.enl</database><source-app name="EndNote" version="16.0">EndNote</source-app><rec-number>31</rec-number><foreign-keys><key app="EN" db-id="0wtxswe0cwwvd8esx9pps2wf2rxxst90w9zs">31</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Kryger, Mille B. L.</style></author><author><style face="normal" font="default" size="100%">Smith, Anton A. 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