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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A Novel Loading Method for Doxycycline Liposomes for Intracellular Drug Delivery: Characterization of In Vitro and In Vivo Release Kinetics and Efficacy in a J774A.1 Cell Line Model of <italic>Mycobacterium smegmatis</italic> Infection<xref ref-type="fn" rid="FN3"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic></sup></xref></title><author><name sortKey="Franklin, Rebekah K" sort="Franklin, Rebekah K" uniqKey="Franklin R" first="Rebekah K." last="Franklin">Rebekah K. Franklin</name></author><author><name sortKey="Marcus, Sarah A" sort="Marcus, Sarah A" uniqKey="Marcus S" first="Sarah A." last="Marcus">Sarah A. Marcus</name></author><author><name sortKey="Talaat, Adel M" sort="Talaat, Adel M" uniqKey="Talaat A" first="Adel M." last="Talaat">Adel M. Talaat</name></author><author><name sortKey="Kukanich, Butch K" sort="Kukanich, Butch K" uniqKey="Kukanich B" first="Butch K." last="Kukanich">Butch K. Kukanich</name></author><author><name sortKey="Sullivan, Ruth" sort="Sullivan, Ruth" uniqKey="Sullivan R" first="Ruth" last="Sullivan">Ruth Sullivan</name></author><author><name sortKey="Krugner Higby, Lisa A" sort="Krugner Higby, Lisa A" uniqKey="Krugner Higby L" first="Lisa A." last="Krugner-Higby">Lisa A. Krugner-Higby</name></author><author><name sortKey="Heath, Timothy D" sort="Heath, Timothy D" uniqKey="Heath T" first="Timothy D." last="Heath">Timothy D. Heath</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26033620</idno><idno type="pmc">4518064</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518064</idno><idno type="RBID">PMC:4518064</idno><idno type="doi">10.1124/dmd.115.063602</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000017</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000017</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A Novel Loading Method for Doxycycline Liposomes for Intracellular Drug Delivery: Characterization of In Vitro and In Vivo Release Kinetics and Efficacy in a J774A.1 Cell Line Model of <italic>Mycobacterium smegmatis</italic> Infection<xref ref-type="fn" rid="FN3"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic></sup></xref></title><author><name sortKey="Franklin, Rebekah K" sort="Franklin, Rebekah K" uniqKey="Franklin R" first="Rebekah K." last="Franklin">Rebekah K. Franklin</name></author><author><name sortKey="Marcus, Sarah A" sort="Marcus, Sarah A" uniqKey="Marcus S" first="Sarah A." last="Marcus">Sarah A. Marcus</name></author><author><name sortKey="Talaat, Adel M" sort="Talaat, Adel M" uniqKey="Talaat A" first="Adel M." last="Talaat">Adel M. Talaat</name></author><author><name sortKey="Kukanich, Butch K" sort="Kukanich, Butch K" uniqKey="Kukanich B" first="Butch K." last="Kukanich">Butch K. Kukanich</name></author><author><name sortKey="Sullivan, Ruth" sort="Sullivan, Ruth" uniqKey="Sullivan R" first="Ruth" last="Sullivan">Ruth Sullivan</name></author><author><name sortKey="Krugner Higby, Lisa A" sort="Krugner Higby, Lisa A" uniqKey="Krugner Higby L" first="Lisa A." last="Krugner-Higby">Lisa A. Krugner-Higby</name></author><author><name sortKey="Heath, Timothy D" sort="Heath, Timothy D" uniqKey="Heath T" first="Timothy D." last="Heath">Timothy D. Heath</name></author></analytic><series><title level="j">Drug Metabolism and Disposition</title><idno type="ISSN">0090-9556</idno><idno type="eISSN">1521-009X</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Doxycycline (doxy) is used in treating intracellular and extracellular infections. Liposomal (LE) antibiotics allow low-frequency dosing and extended efficacy compared with standard (STD) formulations. We developed a novel sulfuric acid–loading method for doxycycline liposomes (LE-doxy). We hypothesized that a single s.c. injection of LE-doxy would be detectable in serum for at least 2 weeks at concentrations equal to or better than STD-doxy and would be bactericidal in an in vitro <italic>Mycobacterium smegmatis</italic> infection of J774A.1 macrophage cells. Liposomes were encapsulated by sulfuric acid gradient loading, and release kinetics were performed in vitro and in vivo. LE-doxy made using 8.25 mg/ml doxycycline loaded for 24 hours achieved 97.77% capture in 1,2-dipalmitoyl-<italic>sn</italic>-glycero-3-phosphocholine (DPPC) and 43.87% in sphingomyelin (sphing). Rats were injected s.c. with 50 mg/kg LE-doxy or 5 mg/kg STD-doxy, and serial blood samples were collected. Pharmacokinetics were analyzed using high-performance liquid chromatography. Liver and injection site skin samples were collected at euthanasia (4 weeks postinjection). Minimal histologic tissue reactions occurred after injection of STD (nonliposomal), DPPC, or sphing-doxy. DPPC-doxy had slightly faster in vitro leakage than sphing liposomes, although both were detectable at 264 hours. The mean residence time for DPPC was the highest (111.78 hours), followed by sphing (56.00 hours) and STD (6.86 hours). DPPC and sphing-doxy were detectable at 0.2 <italic>μ</italic>g/ml in serum at 336 hours postadministration. LE-doxy was not toxic to J774A.1 cells in vitro and produced inhibition of viable <italic>Mycobacterium smegmatis</italic> at 24 and 48 hours. LE-doxy will require further testing in in vivo infection models.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Drug Metab Dispos</journal-id><journal-id journal-id-type="iso-abbrev">Drug Metab. Dispos</journal-id><journal-id journal-id-type="hwp">dmd</journal-id><journal-id journal-id-type="pmc">Drug Metab Dispos</journal-id><journal-id journal-id-type="publisher-id">DMD</journal-id><journal-title-group><journal-title>Drug Metabolism and Disposition</journal-title></journal-title-group><issn pub-type="ppub">0090-9556</issn><issn pub-type="epub">1521-009X</issn><publisher><publisher-name>The American Society for Pharmacology and Experimental Therapeutics</publisher-name><publisher-loc>Bethesda, MD</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26033620</article-id><article-id pub-id-type="pmc">4518064</article-id><article-id pub-id-type="publisher-id">DMD_063602</article-id><article-id pub-id-type="doi">10.1124/dmd.115.063602</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group></article-categories><title-group><article-title>A Novel Loading Method for Doxycycline Liposomes for Intracellular Drug Delivery: Characterization of In Vitro and In Vivo Release Kinetics and Efficacy in a J774A.1 Cell Line Model of <italic>Mycobacterium smegmatis</italic> Infection<xref ref-type="fn" rid="FN3"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic></sup></xref></article-title><alt-title alt-title-type="short">Loading Liposome Doxycycline Pharmacokinetics Efficacy</alt-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Franklin</surname><given-names>Rebekah K.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Marcus</surname><given-names>Sarah A.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Talaat</surname><given-names>Adel M.</given-names></name></contrib><contrib contrib-type="author"><name><surname>KuKanich</surname><given-names>Butch K.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Sullivan</surname><given-names>Ruth</given-names></name></contrib><contrib contrib-type="author"><name><surname>Krugner-Higby</surname><given-names>Lisa A.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Heath</surname><given-names>Timothy D.</given-names></name></contrib><aff id="aff1">Pharmacology, Clinical, Analytical, and Toxicological Services and the Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas (B.K.K.); and Departments of Surgical Sciences (L.A.K.-H.), Pathobiological Sciences (R.S.), and Comparative Biosciences (A.M.T., S.A.M.); School of Veterinary Medicine (R.S.); School of Pharmacy (T.D.H.); and Research Animal Resources Center, University of Wisconsin, Madison, Wisconsin (R.K.F., L.A.K.-H., R.S.)</aff></contrib-group><author-notes><corresp id="cor1"><bold>Address correspondence to:</bold> Rebekah K. Franklin, <addr-line>396 Enzyme Institute, 1710 University Ave., Madison, WI 53726.</addr-line> E-mail: <email>franklin@rarc.wisc.edu</email></corresp></author-notes><pub-date pub-type="ppub"><month>8</month><year>2015</year></pub-date><pub-date pub-type="epub"><month>8</month><year>2015</year></pub-date><pub-date pub-type="pmc-release"><day>1</day><month>8</month><year>2016</year></pub-date><pmc-comment> PMC Release delay is 12 months and
0 days and was based on the
<volume>43</volume><issue>8</issue><fpage>1236</fpage><lpage>1245</lpage><history><date date-type="received"><day>29</day><month>1</month><year>2015</year></date><date date-type="accepted"><day>01</day><month>6</month><year>2015</year></date></history><permissions><copyright-statement>Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics</copyright-statement><copyright-year>2015</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="dmd.115.063602.pdf"></self-uri><abstract><p>Doxycycline (doxy) is used in treating intracellular and extracellular infections. Liposomal (LE) antibiotics allow low-frequency dosing and extended efficacy compared with standard (STD) formulations. We developed a novel sulfuric acid–loading method for doxycycline liposomes (LE-doxy). We hypothesized that a single s.c. injection of LE-doxy would be detectable in serum for at least 2 weeks at concentrations equal to or better than STD-doxy and would be bactericidal in an in vitro <italic>Mycobacterium smegmatis</italic> infection of J774A.1 macrophage cells. Liposomes were encapsulated by sulfuric acid gradient loading, and release kinetics were performed in vitro and in vivo. LE-doxy made using 8.25 mg/ml doxycycline loaded for 24 hours achieved 97.77% capture in 1,2-dipalmitoyl-<italic>sn</italic>-glycero-3-phosphocholine (DPPC) and 43.87% in sphingomyelin (sphing). Rats were injected s.c. with 50 mg/kg LE-doxy or 5 mg/kg STD-doxy, and serial blood samples were collected. Pharmacokinetics were analyzed using high-performance liquid chromatography. Liver and injection site skin samples were collected at euthanasia (4 weeks postinjection). Minimal histologic tissue reactions occurred after injection of STD (nonliposomal), DPPC, or sphing-doxy. DPPC-doxy had slightly faster in vitro leakage than sphing liposomes, although both were detectable at 264 hours. The mean residence time for DPPC was the highest (111.78 hours), followed by sphing (56.00 hours) and STD (6.86 hours). DPPC and sphing-doxy were detectable at 0.2 <italic>μ</italic>g/ml in serum at 336 hours postadministration. LE-doxy was not toxic to J774A.1 cells in vitro and produced inhibition of viable <italic>Mycobacterium smegmatis</italic> at 24 and 48 hours. LE-doxy will require further testing in in vivo infection models.</p></abstract><counts><page-count count="10"></page-count></counts><custom-meta-group><custom-meta><meta-name> DJS Export </meta-name><meta-value>v1</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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