Lymphatic delivery of etanercept via nanotopography improves response to collagen-induced arthritis
Identifieur interne : 000425 ( Main/Exploration ); précédent : 000424; suivant : 000426Lymphatic delivery of etanercept via nanotopography improves response to collagen-induced arthritis
Auteurs : Melissa B. Aldrich [États-Unis] ; Fred C. Velasquez [États-Unis] ; Sunkuk Kwon [États-Unis] ; Ali Azhdarinia [États-Unis] ; Kenneth Pinkston [États-Unis] ; Barrett R. Harvey [États-Unis] ; Wenyaw Chan [États-Unis] ; John C. Rasmussen [États-Unis] ; Russell F. Ross [États-Unis] ; Caroline E. Fife [États-Unis] ; E. M. Sevick-Muraca [États-Unis]Source :
- Arthritis Research & Therapy [ 1478-6354 ] ; 2017.
Abstract
Evidence suggests lymphatic function mediates local rheumatoid arthritis (RA) flares. Yet biologics that target the immune system are dosed systemically via the subcutaneous (SC) administration route, thereby inefficiently reaching local lymphatic compartments. Nanotopography has previously been shown to disrupt tight cellular junctions, potentially enhancing local lymphatic delivery and potentially improving overall therapeutic efficacy.
We first characterized nanotopography (SOFUSA™) delivery of an anti-TNF drug, etanercept, by comparing pharmacokinetic profiles to those obtained by conventional SC, intravenous (IV), and intradermal (ID) routes of administration, and assessed uptake of radiolabeled etanercept in draining lymph nodes (LNs) in single dosing studies. We then compared etanercept efficacy in a progressive rat model of collagen-induced arthritis (CIA), administered systemically via SC route of administration; via the regional lymphatics through ID delivery; or through a nanotopography (SOFUSA™) device at 10, 12, and 14 days post CIA induction. Measurements of hind limb swelling and near-infrared fluorescence (NIRF) imaging of afferent lymph pumping function and reflux were conducted on days 11, 13, and 18 post CIA induction and compared to untreated CIA animals. Univariate and multivariate analysis of variance were used to compare the group differences for percentage swelling and lymphatic contractile activity.
Even though all three modes of administration delivered an equal amount of etanercept, SOFUSA™ delivery resulted in increased lymphatic pumping and significantly reduced swelling as compared to untreated, ID, and SC groups. Pharmacokinetic profiles in serum and LN uptake studies showed that using the nanotopography device resulted in the greatest uptake and retention in draining LNs.
Locoregional lymphatic delivery of biologics that target the immune system may have more favorable pharmacodynamics than SC or IV administration. Nanotopography may provide a more efficient method for delivery of anti-TNF drugs to reverse impairment of lymphatic function and reduce swelling associated with RA flares.
The online version of this article (doi:10.1186/s13075-017-1323-z) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s13075-017-1323-z
PubMed: 28566090
PubMed Central: 5452411
Affiliations:
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Aldrich</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9206 2401</institution-id><institution-id institution-id-type="GRID">grid.267308.8</institution-id><institution></institution><institution>The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center,</institution></institution-wrap>Houston, TX 77030 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Houston</wicri:cityArea></affiliation></author><author><name sortKey="Velasquez, Fred C" sort="Velasquez, Fred C" uniqKey="Velasquez F" first="Fred C." last="Velasquez">Fred C. Velasquez</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9206 2401</institution-id><institution-id institution-id-type="GRID">grid.267308.8</institution-id><institution></institution><institution>The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center,</institution></institution-wrap>Houston, TX 77030 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Houston</wicri:cityArea></affiliation></author><author><name sortKey="Kwon, Sunkuk" sort="Kwon, Sunkuk" uniqKey="Kwon S" first="Sunkuk" last="Kwon">Sunkuk Kwon</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9206 2401</institution-id><institution-id institution-id-type="GRID">grid.267308.8</institution-id><institution></institution><institution>The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center,</institution></institution-wrap>Houston, TX 77030 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Houston</wicri:cityArea></affiliation></author><author><name sortKey="Azhdarinia, Ali" sort="Azhdarinia, Ali" uniqKey="Azhdarinia A" first="Ali" last="Azhdarinia">Ali Azhdarinia</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9206 2401</institution-id><institution-id institution-id-type="GRID">grid.267308.8</institution-id><institution></institution><institution>The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center,</institution></institution-wrap>Houston, TX 77030 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Houston</wicri:cityArea></affiliation></author><author><name sortKey="Pinkston, Kenneth" sort="Pinkston, Kenneth" uniqKey="Pinkston K" first="Kenneth" last="Pinkston">Kenneth Pinkston</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9206 2401</institution-id><institution-id institution-id-type="GRID">grid.267308.8</institution-id><institution></institution><institution>The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center,</institution></institution-wrap>Houston, TX 77030 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Houston</wicri:cityArea></affiliation></author><author><name sortKey="Harvey, Barrett R" sort="Harvey, Barrett R" uniqKey="Harvey B" first="Barrett R." last="Harvey">Barrett R. Harvey</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9206 2401</institution-id><institution-id institution-id-type="GRID">grid.267308.8</institution-id><institution></institution><institution>The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center,</institution></institution-wrap>Houston, TX 77030 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Houston</wicri:cityArea></affiliation></author><author><name sortKey="Chan, Wenyaw" sort="Chan, Wenyaw" uniqKey="Chan W" first="Wenyaw" last="Chan">Wenyaw Chan</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9206 2401</institution-id><institution-id institution-id-type="GRID">grid.267308.8</institution-id><institution>Department of Biostatistics, The School of Public Health,</institution><institution>The University of Texas Health Science Center,</institution></institution-wrap>Houston, TX 77030 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Houston</wicri:cityArea></affiliation></author><author><name sortKey="Rasmussen, John C" sort="Rasmussen, John C" uniqKey="Rasmussen J" first="John C." last="Rasmussen">John C. Rasmussen</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9206 2401</institution-id><institution-id institution-id-type="GRID">grid.267308.8</institution-id><institution></institution><institution>The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center,</institution></institution-wrap>Houston, TX 77030 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Houston</wicri:cityArea></affiliation></author><author><name sortKey="Ross, Russell F" sort="Ross, Russell F" uniqKey="Ross R" first="Russell F." last="Ross">Russell F. Ross</name><affiliation wicri:level="2"><nlm:aff id="Aff3">Kimberly Clark Corporation, Atlanta, GA USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Géorgie (États-Unis)</region></placeName><wicri:cityArea>Kimberly Clark Corporation, Atlanta</wicri:cityArea></affiliation></author><author><name sortKey="Fife, Caroline E" sort="Fife, Caroline E" uniqKey="Fife C" first="Caroline E." last="Fife">Caroline E. Fife</name><affiliation wicri:level="2"><nlm:aff id="Aff4">The Wound Care Clinic, CHI St. Luke’s Health, The Woodlands Hospital, The Woodlands, TX 77382 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>The Wound Care Clinic, CHI St. Luke’s Health, The Woodlands Hospital, The Woodlands</wicri:cityArea></affiliation></author><author><name sortKey="Sevick Muraca, E M" sort="Sevick Muraca, E M" uniqKey="Sevick Muraca E" first="E. M." last="Sevick-Muraca">E. M. Sevick-Muraca</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9206 2401</institution-id><institution-id institution-id-type="GRID">grid.267308.8</institution-id><institution></institution><institution>The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center,</institution></institution-wrap>Houston, TX 77030 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Houston</wicri:cityArea></affiliation></author></analytic><series><title level="j">Arthritis Research & Therapy</title><idno type="ISSN">1478-6354</idno><idno type="eISSN">1478-6362</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Evidence suggests lymphatic function mediates local rheumatoid arthritis (RA) flares. Yet biologics that target the immune system are dosed systemically via the subcutaneous (SC) administration route, thereby inefficiently reaching local lymphatic compartments. Nanotopography has previously been shown to disrupt tight cellular junctions, potentially enhancing local lymphatic delivery and potentially improving overall therapeutic efficacy.</p></sec><sec><title>Method</title><p>We first characterized nanotopography (SOFUSA™) delivery of an anti-TNF drug, etanercept, by comparing pharmacokinetic profiles to those obtained by conventional SC, intravenous (IV), and intradermal (ID) routes of administration, and assessed uptake of radiolabeled etanercept in draining lymph nodes (LNs) in single dosing studies. We then compared etanercept efficacy in a progressive rat model of collagen-induced arthritis (CIA), administered systemically via SC route of administration; via the regional lymphatics through ID delivery; or through a nanotopography (SOFUSA™) device at 10, 12, and 14 days post CIA induction. Measurements of hind limb swelling and near-infrared fluorescence (NIRF) imaging of afferent lymph pumping function and reflux were conducted on days 11, 13, and 18 post CIA induction and compared to untreated CIA animals. Univariate and multivariate analysis of variance were used to compare the group differences for percentage swelling and lymphatic contractile activity.</p></sec><sec><title>Results</title><p>Even though all three modes of administration delivered an equal amount of etanercept, SOFUSA™ delivery resulted in increased lymphatic pumping and significantly reduced swelling as compared to untreated, ID, and SC groups. Pharmacokinetic profiles in serum and LN uptake studies showed that using the nanotopography device resulted in the greatest uptake and retention in draining LNs.</p></sec><sec><title>Conclusions</title><p>Locoregional lymphatic delivery of biologics that target the immune system may have more favorable pharmacodynamics than SC or IV administration. Nanotopography may provide a more efficient method for delivery of anti-TNF drugs to reverse impairment of lymphatic function and reduce swelling associated with RA flares.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1186/s13075-017-1323-z) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Emery, P" uniqKey="Emery P">P Emery</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alitalo, K" uniqKey="Alitalo K">K Alitalo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baluk, P" uniqKey="Baluk P">P Baluk</name></author><author><name sortKey="Fuxe, J" uniqKey="Fuxe J">J Fuxe</name></author><author><name sortKey="Hashizume, H" uniqKey="Hashizume H">H Hashizume</name></author><author><name sortKey="Romano, T" uniqKey="Romano T">T 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Melissa B" uniqKey="Aldrich M" first="Melissa B." last="Aldrich">Melissa B. Aldrich</name></region><name sortKey="Azhdarinia, Ali" sort="Azhdarinia, Ali" uniqKey="Azhdarinia A" first="Ali" last="Azhdarinia">Ali Azhdarinia</name><name sortKey="Chan, Wenyaw" sort="Chan, Wenyaw" uniqKey="Chan W" first="Wenyaw" last="Chan">Wenyaw Chan</name><name sortKey="Fife, Caroline E" sort="Fife, Caroline E" uniqKey="Fife C" first="Caroline E." last="Fife">Caroline E. Fife</name><name sortKey="Harvey, Barrett R" sort="Harvey, Barrett R" uniqKey="Harvey B" first="Barrett R." last="Harvey">Barrett R. Harvey</name><name sortKey="Kwon, Sunkuk" sort="Kwon, Sunkuk" uniqKey="Kwon S" first="Sunkuk" last="Kwon">Sunkuk Kwon</name><name sortKey="Pinkston, Kenneth" sort="Pinkston, Kenneth" uniqKey="Pinkston K" first="Kenneth" last="Pinkston">Kenneth Pinkston</name><name sortKey="Rasmussen, John C" sort="Rasmussen, John C" uniqKey="Rasmussen J" first="John C." last="Rasmussen">John C. Rasmussen</name><name sortKey="Ross, Russell F" sort="Ross, Russell F" uniqKey="Ross R" first="Russell F." last="Ross">Russell F. Ross</name><name sortKey="Sevick Muraca, E M" sort="Sevick Muraca, E M" uniqKey="Sevick Muraca E" first="E. M." last="Sevick-Muraca">E. M. Sevick-Muraca</name><name sortKey="Velasquez, Fred C" sort="Velasquez, Fred C" uniqKey="Velasquez F" first="Fred C." last="Velasquez">Fred C. Velasquez</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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