Hydrogen-bonding layer-by-layer assembled biodegradable polymeric micelles as drug delivery vehicles from surfaces
Hydrogen-bonding layer-by-layer assembled biodegradable polymeric micelles as drug delivery vehicles from surfaces
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DOI：
10.1021/nn700408z
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发表时间：
2008-02-01
期刊：
影响因子：
17.1
通讯作者：
Hammond, Paula T.
中科院分区：
文献类型：
--
作者：
Kim, Byeong-Su;Park, Sang Wook;Hammond, Paula T.
我们提出的集成的两亲性嵌段共聚物胶束作为纳米尺寸的车辆内的疏水性药物的层-层（LBL）膜使用交替的氢键相互作用作为驱动力组装的第一次，从而使药物的掺入和pH敏感的释放。该膜是基于聚（丙烯酸）（PAA）作为氢键供体和可生物降解的聚（环氧乙烷）-嵌段-聚（是-己内酯的一个元素）（PEO-b-PCL）胶束作为氢键受体组装在酸性条件下时之间的氢键。通过利用氢键膜在疏水表面上的弱相互作用，可以产生这些材料的柔性自支撑膜。分离出厚度为3.1 μ m的（PEO-b-PCL/PAA）（60）的独立胶束LbL膜，允许使用透射电子显微镜和差示扫描量热法进一步表征本体膜性质，包括形态和相变。由于用于构建多层膜的氢键的敏感性，在暴露于生理条件时，膜可以快速解构以释放胶束。然而，我们也可以通过热诱导的酸酐键交联PAA中的羧酸基团成功地控制膜解构的速率，这延迟了药物释放到周围介质中，以实现持续释放多天。为了证明递送活性治疗剂的功效，使用针对金黄色葡萄球菌的体外Kirby-Bauer测定来说明载药胶束LbL膜可释放显著量的活性抗菌药物三氯生以抑制细菌生长。由于疏水治疗剂的胶束包封不需要特定的化学相互作用，我们相信这种非共价方法提供了一种新的途径，将活性小，不带电，疏水治疗剂整合到LbL薄膜的生物和生物医学涂层。
We present the integration of amphiphilic block copolymer micelles as nanometer-sized vehicles for hydrophobic drugs within layer-by-layer (LbL) films using alternating hydrogen bond interactions as the driving force for assembly for the first time, thus enabling the incorporation of drugs and pH-sensitive release. The film was constructed based on the hydrogen bonding between poly(acrylic acid) (PAA) as an H-bond donor and biodegradable poly(ethylene oxide)-block-poly(is an element of-caprolactone) (PEO-b-PCL) micelles as the H-bond acceptor when assembled under acidic conditions. By taking advantage of the weak interactions of the hydrogen-bonded film on hydrophobic surfaces, it is possible to generate flexible free-standing films of these materials. A freestanding micelle LbL film of (PEO-b-PCL/PAA)(60) with a thickness of 3.1 mu m was isolated, allowing further characterization of the bulk film properties, including morphology and phase transitions, using transmission electron microscopy and differential scanning calorimetry. Because of the sensitive nature of the hydrogen bonding employed to build the multilayers, the film can be rapidly deconstructed to release micelles upon exposure to physiological conditions. However, we could also successfully control the rate of film deconstruction by cross-linking carboxylic acid groups in PAA through thermally induced anhydride linkages, which retard the drug release to the surrounding medium to enable sustained release over multiple days. To demonstrate efficacy in delivering active therapeutics, in vitro Kirby-Bauer assays against Staphylococcus aureus were used to illustrate that the drug-loaded micelle LbL film can release significant amounts of an active antibacterial drug, triclosan, to inhibit the growth of bacteria. Because the micellar encapsulation of hydrophobic therapeutics does not require specific chemical interactions, we believe this noncovalent approach provides a new route to integrating active small, uncharged, and hydrophobic therapeutics into LbL thin films for biological and biomedical coatings.