Extended release antibacterial layer-by-layer films incorporating linear-dendritic block copolymer micelles
Extended release antibacterial layer-by-layer films incorporating linear-dendritic block copolymer micelles
复制标题
DOI：
10.1021/cm070981f
复制
发表时间：
2007-11-13
影响因子：
8.6
通讯作者：
Hammond, Paula T.
中科院分区：
文献类型：
--
作者：
Nguyen, Phuong M.;Zacharia, Nicole S.;Hammond, Paula T.
静电逐层（LBL）组装方法在薄膜药物递送领域提供了很大的潜力;然而，由于加工技术是水基的，因此很少有人提出将疏水分子掺入这些膜中的策略。在这里，我们创建了一个LBL膜，能够通过与线性树枝状嵌段共聚物胶束封装在高负载的疏水性药物，并证明了第一次释放时间的疏水性抗菌剂在一段时间内的几个星期，一个显着的改善比其他n-ticellecapsulated薄膜的报告，释放时间为几分钟。两亲性线性-树枝状嵌段共聚物由聚（环氧丙烷）（PPO）和聚（酰胺基胺）（PANIAM）组成，聚（环氧丙烷）（PPO）形成疏水核，产生用于疏水药物包封的隔室，聚（酰胺基胺）（PANIAM）形成胶束的外冠。PAMAM是聚阳离子的，使得能够用带负电荷的聚（丙烯酸）（PAA）进行LbL沉积。稳定的PPO-PAMAM胶束纳入LbL膜包封的疏水性，三氯生，其具有高达80- 90%的负载容量。膜厚度和紫外-可见光测量证实了LbL膜的形成和三氯生掺入膜中。PPO-PAMAMIPAA薄膜与芘的荧光测量表明在膜中的疏水域的存在下。GISAXS显示在平行于膜基底的方向上约10.5 nm的规则间距，这与水溶液中的PPO-PAMAM胶束的尺寸大致相同。基于元素分析和TGA的体积分数测量证实了GISAXS数据。体外释放研究显示三氯生的释放时间长达数周，对金黄色葡萄球菌进行了Kirby Bauer试验，证明释放的药物仍然具有抑制细菌生长的活性。
The electrostatic layer-by-layer (LbL) assembly approach offers large potential in the area of drug delivery from thin films; however, because the processing technique is aqueous-based, there have been few strategies proposed to incorporate hydrophobic molecules into these films. Here we create an LbL film that is capable of incorporating hydrophobic drug at high loadings via encapsulation with lineardendritic block copolymer micelles and demonstrate for the first time release times of a hydrophobic antibacterial agent over a period of several weeks-a significant improvement over reports of other n-ticelleencapsulated thin films with release times of several minutes. The amphiphilic linear-dendritic block copolymer is composed of poly(propylene oxide) (PPO), which forms the hydrophobic core creating the compartment for hydrophobic drug encapsulation, and poly(amidoamine) (PANIAM), which forms the outer corona of the micelle. The PAMAM is polycationic, enabling LbL deposition with negatively charged poly(acrylic acid) (PAA). The stable PPO-PAMAM micelles incorporated into the LbL films encapsulated a hydrophobic bactericide, triclosan, which have loading capacities as high as 80-90%. Film thickness and UV-vis measurements confirm the formation of the LbL film and incorporation of triclosan into the film. Fluorescence measurements of PPO-PAMAMIPAA films with pyrene indicated the presence of hydrophobic domains in the film. GISAXS revealed regular spacing of approximately 10.5 nm in the direction parallel to the film substrate, which is approximately the same size as the PPO-PAMAM micelles in aqueous solution. Volume fraction measurements based on elemental analysis and TGA confirm the GISAXS data. An in vitro release study revealed long release times of triclosan on the order of weeks, and a Kirby Bauer test was performed on Staphylococcus aureus, demonstrating that the drug released was still active to inhibit the growth of bacteria.