کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
7064 530 2012 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Dendrimer-based targeted intravitreal therapy for sustained attenuation of neuroinflammation in retinal degeneration
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
Dendrimer-based targeted intravitreal therapy for sustained attenuation of neuroinflammation in retinal degeneration
چکیده انگلیسی

Retinal neuroinflammation, mediated by activated microglia, plays a key role in the pathogenesis of photoreceptor and retinal pigment epithelial cell loss in age-related macular degeneration and retinitis pigmentosa. Targeted drug therapy for attenuation of neuroinflammation in the retina was explored using hydroxyl-terminated polyamidoamine (PAMAM) dendrimer-drug conjugate nanodevices. We show that, upon intravitreal administration, PAMAM dendrimers selectively localize within activated outer retinal microglia in two rat models of retinal degeneration, but not in the retina of healthy controls. This pathology-dependent biodistribution was exploited for drug delivery, by covalently conjugating fluocinolone acetonide to the dendrimer. The conjugate released the drug in a sustained manner over 90 days. In vivo efficacy was assessed using the Royal College of Surgeons (RCS) rat retinal degeneration model over a four-week period when peak retinal degeneration occurs. One intravitreal injection of 1 μg of FA conjugated to 7 μg of the dendrimer was able to arrest retinal degeneration, preserve photoreceptor outer nuclear cell counts, and attenuate activated microglia, for an entire month. These studies suggest that PAMAM dendrimers (with no targeting ligands) have an intrinsic ability to selectively localize in activated microglia, and can deliver drugs inside these cells for a sustained period for the treatment of retinal neuroinflammation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 33, Issue 3, January 2012, Pages 979–988
نویسندگان
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