Copolymeric nanofilm platform for controlled and localized therapeutic delivery
Copolymeric nanofilm platform for controlled and localized therapeutic delivery
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DOI：
10.1021/nn7000917
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发表时间：
2008-01-01
期刊：
影响因子：
17.1
通讯作者：
Ho, Dean
中科院分区：
文献类型：
--
作者：
Chow, Edward Kai-Hua;Pierstorff, Erik;Ho, Dean
诸如嵌段共聚物膜的纳米材料为细胞询问和生物模拟提供了平台。它们的仿生特性是基于亲水和疏水单元的先天拥有，这使得它们能够与广泛的治疗材料整合。因此，它们可以被设计用于纳米医学中的特定应用，包括受控/局部药物递送。在这里，我们描述了一种方法的功能化的聚甲基恶唑啉-聚二甲基硅氧烷-聚甲基恶唑啉（PMOXA-PDMS-PMOXA）嵌段共聚物与抗炎分子开发共聚物-治疗的杂交，有效地赋予生物功能的通用合成纳米膜基质和创建一个平台的抗炎药物输送系统。利用自组装和Langmuir-Blodgett沉积方法，我们将共聚物与地塞米松（Dex）（一种抗炎糖皮质激素受体激动剂）混合。通过表面压力等温线和荧光显微镜证实了共聚物与药物的成功混合。此外，在每层4 nm厚，比常规药物递送涂层薄几个数量级，这些地塞米松-共聚物混合物（PolyDex）抑制炎性细胞因子/信号传导元件白细胞介素6（IL-6）、白细胞介素12（IL-12）、肿瘤坏死因子α（TNF α）、诱导型一氧化氮合酶（iNOS）和干扰素γ诱导蛋白（IP-10）的体外表达。最后，PolyDex在体内保持了其抗炎特性，这通过使用苏木精/伊红和巨噬细胞特异性染色（使用CD 11b）进行组织成像的打孔活检得到证实。因此，我们证明PolyDex可用作局部高效药物-共聚物复合物，用于主动治疗递送以提供抗炎保护，或用作广泛药物洗脱能力的平台材料。
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 (TNF alpha), 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.