کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8716162 | 1587879 | 2018 | 23 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
RNA Aptamer Delivery through Intact Human Skin
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
امراض پوستی
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چکیده انگلیسی
It is generally recognized that only relatively small molecular weight (typically < ⼠500 Da) drugs can effectively permeate through intact stratum corneum. Here, we challenge this orthodoxy using a 62-nucleotide (molecular weight = 20,395 Da) RNA-based aptamer, highly specific to the human IL-23 cytokine, with picomolar activity. Results demonstrate penetration of the aptamer into freshly excised human skin using two different fluorescent labels. A dual hybridization assay quantified aptamer from the epidermis and dermis, giving levels far exceeding the cellular half maximal inhibitory concentration values (>100,000-fold), and aptamer integrity was confirmed using an oligonucleotide precipitation assay. A T helper 17 response was stimulated in freshly excised human skin resulting in significantly upregulated IL-17f, and IL-22; topical application of the IL-23 aptamer decreased both IL-17f and IL-22 by approximately 45% but did not result in significant changes to IL-23 mRNA levels, confirming that the aptamer did not globally suppress mRNA levels. This study demonstrates that very-large-molecular-weight RNA aptamers can permeate across the intact human skin barrier to therapeutically relevant levels into both the epidermis and dermis and that the skin-penetrating aptamer retains its biologically active conformational structure capable of binding to endogenous IL-23.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Investigative Dermatology - Volume 138, Issue 2, February 2018, Pages 282-290
Journal: Journal of Investigative Dermatology - Volume 138, Issue 2, February 2018, Pages 282-290
نویسندگان
Jon D. Lenn, Jessica Neil, Christine Donahue, Kellie Demock, Caitlin Vestal Tibbetts, Javier Cote-Sierra, Susan H. Smith, David Rubenstein, Jean-Philippe Therrien, P. Shannon Pendergrast, Jason Killough, Marc B. Brown, Adrian C. Williams,