کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6451021 1416153 2017 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Transport patterns of anti-TNF-α in burn wounds: Therapeutic implications of hyaluronic acid conjugation
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
Transport patterns of anti-TNF-α in burn wounds: Therapeutic implications of hyaluronic acid conjugation
چکیده انگلیسی

A central complication in burn injuries is progression of the zone of necrosis, which is associated with intense inflammatory responses. Conjugation of monoclonal antibodies against tumor necrosis factor-α (TNF-α), a central mediator of inflammation, to high molecular weight hyaluronic acid (HA) has been shown to be an effective treatment in reducing secondary necrosis in rodent models of deep partial-thickness burns. Here the transport of conjugated and non-conjugated antibodies in burn injuries was investigated to explore the effects of antibody tethering on the spatiotemporal distribution of anti-TNF-α. Diffusion constants were measured in solution and in type I collagen gels in vitro using fluorescence correlation spectroscopy to provide quantitative comparisons of the effects of conjugation. It is shown that the HA significantly increased the antibody residence time in the superficial region at 24 h in burn injuries, which strongly correlated with the pattern of inflammatory cell infiltrate in the tissue. A transport model was used to fit the results of antibody distribution in the tissue based on fluorescence correlation spectroscopy measurements, resulting in estimates for effective diffusion constants that demonstrate the effects of HA conjugation on the biodistribution of therapeutic proteins. These results demonstrate that tuning residence time of therapeutic proteins can be an effective strategy in regulating the inflammatory response associated with acute injuries.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 114, January 2017, Pages 10-22
نویسندگان
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