Copolymeric Nanofilm Platform for Controlled and Localized Therapeutic Delivery

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• 作者：Edward Kai-Hua Chow ; Erik Pierstorff ; Genhong Cheng ; Dean Ho
• 刊名：ACS Nano
• 出版年：2008
• 出版时间：January 22, 2008
• 年：2008
• 卷：2
• 期：1
• 页码：33-40
• 全文大小：357K
• 年卷期：0
• ISSN：1936-086X

文摘

Nanomaterials such as block copolymeric membranes provide a platform for both cellular interrogation and biological mimicry. Their biomimetic properties are based upon the innate possession of hydrophilic and hydrophobic units that enable their integration with a broad range of therapeutic materials. As such, they can be engineered for specific applications in nanomedicine, including controlled/localized drug delivery. Here we describe a method for the functionalization of the polymethyloxazoline−polydimethylsiloxane−polymethyloxazoline (PMOXA−PDMS−PMOXA) block copolymer with anti-inflammatory molecules to develop copolymer−therapeutic hybrids, effectively conferring biological functionality to a versatile synthetic nanomembrane matrix and creating a platform for an anti-inflammatory drug delivery system. Utilizing self-assembly and Langmuir–Blodgett deposition methods, we mixed copolymers with dexamethasone (Dex), an anti-inflammatory glucocorticoid receptor agonist. The successful mixing of the copolymer with the drug was confirmed by surface pressure isotherms and fluorescence microscopy. Furthermore, at 4 nm thick per layer, orders of magnitude thinner than conventional drug delivery coatings, these dexamethasone−copolymer mixtures (PolyDex) suppressed in vitro expression of the inflammatory cytokines/signaling elements interleukin 6 (IL-6), interleukin 12 (IL-12), tumor necrosis factor alpha (TNFα), inducible nitric oxide synthase (iNOS), and interferon gamma inducible protein (IP-10). Finally, PolyDex maintained its anti-inflammatory properties in vivo confirmed through punch biopsies with tissue imagery via hematoxylin/eosin and macrophage specific staining using CD11b. Thus, we demonstrated that PolyDex may be utilized as a localized, highly efficient drug−copolymer composite for active therapeutic delivery to confer anti-inflammatory protection or as a platform material for broad drug elution capabilities.