Abstract:
BACKGROUND: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. METHOD: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. RESULTS: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. CONCLUSIONS: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.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Aldrich MB,Velasquez FC,Kwon S,Azhdarinia A,Pinkston K,Harvey BR,Chan W,Rasmussen JC,Ross RF,Fife CE,Sevick-Muraca EMdoi
10.1186/s13075-017-1323-zsubject
Has Abstractpub_date
2017-05-31 00:00:00pages
116issue
1eissn
1478-6354issn
1478-6362pii
10.1186/s13075-017-1323-zjournal_volume
19pub_type
杂志文章abstract:INTRODUCTION:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Cardiovascular disease (CVD) is common and a major cause of mortality. Studies on cardiovascular morbidity are abundant, whereas mortality studies focusing on cardiovascular outcomes are scarce. The aim of this study was to investigate cau...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3759
更新日期:2012-01-01 00:00:00
abstract:INTRODUCTION:The purpose of this study was to evaluate and compare the serum levels and local expression of resistin in patients with idiopathic inflammatory myopathies to controls, and to determine the relationship between resistin levels, inflammation and disease activity. METHODS:Serum resistin levels were determin...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3836
更新日期:2012-05-11 00:00:00
abstract::Adverse events of opioids may restrict their use in non-cancer pain. Analysis of the incidence of common adverse events in trials conducted in non-cancer pain has usually been limited to opioids used to treat severe pain according to the WHO three-step ladder. To examine the incidence of common adverse events of opioi...
journal_title:Arthritis research & therapy
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doi:10.1186/ar1782
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/s13075-018-1635-7
更新日期:2018-07-13 00:00:00
abstract:INTRODUCTION:High levels of the oncoprotein survivin may be detected in the majority of patients with early rheumatoid arthritis (RA). Survivin is a sensitive predictor of joint damage and persistent disease activity. Survivin-positive patients are often poor responders to antirheumatic and biological treatment. The ai...
journal_title:Arthritis research & therapy
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doi:10.1186/ar4438
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02313-w
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3778
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
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doi:10.1186/s13075-017-1251-y
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journal_title:Arthritis research & therapy
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doi:10.1186/s13075-020-02365-y
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journal_title:Arthritis research & therapy
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更新日期:2006-01-01 00:00:00
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4370
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3172
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3881
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,meta分析,评审
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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journal_title:Arthritis research & therapy
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doi:10.1186/ar4403
更新日期:2013-01-01 00:00:00
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journal_title:Arthritis research & therapy
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更新日期:2004-01-01 00:00:00
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journal_title:Arthritis research & therapy
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更新日期:2014-07-16 00:00:00
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journal_title:Arthritis research & therapy
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更新日期:2010-01-01 00:00:00