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Silencing of proinflammatory genes targeted to peritoneal-residing macrophages using siRNA encapsulated in biodegradable microspheres

Paper ID Volume ID Publish Year Pages File Format Full-Text
8473 591 2010 10 PDF Available
Title
Silencing of proinflammatory genes targeted to peritoneal-residing macrophages using siRNA encapsulated in biodegradable microspheres
Abstract

One of the more substantial hurdles to be overcome in realizing the exciting potential of siRNA molecules as therapeutic agents for a wide range of diseases is the intact delivery of the active molecule into its target cell. Here, we present a platform for in vitro and in vivo delivery and intracellular release of siRNA in peritoneal macrophages (Mϕs). The delivery platform is based on the encapsulation of siRNA in biodegradable poly(d,l-lactide) (PLA) microspheres, which are targeted to Mϕs by the simple principle of size exclusion. Proof of concept was achieved using siRNAs targeting TNFα and CD86 in macrophages. We show that the release of the siRNA in peritoneal-derived macrophages in vitro occurs intracellularly, and is abrogated by cytochalasin B, a phagocytosis inhibitor. Silencing in these cells is potent and lasts for at least one week. In vivo, we prove that siRNA encapsulated in biodegradable PLA microspheres can be delivered to peritoneal-residing Mϕs and can induce potent silencing of TNFα secretion for at least one week. The PLA microspheres hold great potential for in vivo use, due to their biocompatibility and degradability, and can potentially be used for in vivo immunomodulation of Mϕs for treatment of autoimmune and chronic inflammatory conditions.

Keywords
Biodegradable microspheres; siRNA delivery; Immunomodulation; Macrophage
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Silencing of proinflammatory genes targeted to peritoneal-residing macrophages using siRNA encapsulated in biodegradable microspheres
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 9, March 2010, Pages 2627–2636
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us