Tunable staged release of therapeutics from layer-by-layer coatings with clay interlayer barrier.
Tunable staged release of therapeutics from layer-by-layer coatings with clay interlayer barrier.
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DOI：
10.1016/j.biomaterials.2013.12.009
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发表时间：
2014-03
期刊：
影响因子：
14
通讯作者：
Hammond, Paula T.
中科院分区：
文献类型：
--
作者：
Min, Jouha;Braatz, Richard D.;Hammond, Paula T.
在开发用于医疗装置和组织工程支架的新一代涂层时，需要薄涂层，其提供多种治疗剂的受控顺序释放，同时提供时间依赖性的可调方法和顺序或分阶段释放的可能性。在此，我们证明了开发自组装的基于聚合物的保形涂层的能力，该保形涂层通过使用水基逐层（LbL）方法构建，作为双重用途的仿生植入物表面，其提供交错和/或持续释放的抗生素，然后是用于骨科植入物应用的活性生长因子。该多层涂层由两部分组成：含有骨形态发生蛋白-2（rhBMP-2）的基础骨诱导组分，位于含有庆大霉素（GS）的抗菌组分下方。对于制造真正分层的复合膜与定制的释放行为，我们提出了一种新的策略，实施锂皂石粘土屏障，允许通过控制层间扩散的两个组件的物理分离。单组分GS系统中的粘土屏障有效地阻断了基于扩散的释放，导致推注剂量减少约50%，释放时间增加10倍。在双重治疗复合涂层中，发现顶部GS组分本身是底层rhBMP-2的有效物理屏障，与单组分rhBMP-2系统相比，释放时间增加了一个数量级。锂皂石层间屏障的引入进一步增强了两种药物释放之间的时间间隔，导致rhBMP-2的生理学上更合适的剂量。从复合涂层释放的两种治疗剂在其确定的释放时间范围内保持其功效。这种用于多药物局部递送的新平台可以容易地制造、调整和转化为需要控制多种药物的空间和时间释放曲线的各种植入应用。
In developing new generations of coatings for medical devices and tissue engineering scaffolds, there is a need for thin coatings that provide controlled sequential release of multiple therapeutics while providing a tunable approach to time dependence and the potential for sequential or staged release. Herein, we demonstrate the ability to develop a self-assembled, polymer-based conformal coating, built by using a water-based layer-by-layer (LbL) approach, as a dual-purpose biomimetic implant surface that provides staggered and/or sustained release of an antibiotic followed by active growth factor for orthopedic implant applications. This multilayered coating consists of two parts: a base osteoinductive component containing bone morphogenetic protein-2 (rhBMP-2) beneath an antibacterial component containing gentamicin (GS). For the fabrication of truly stratified composite films with the customized release behavior, we present a new strategy—implementation of laponite clay barriers—that allows for a physical separation of the two components by controlling interlayer diffusion. The clay barriers in a single-component GS system effectively block diffusion-based release, leading to approximately 50% reduction in bolus doses and 10-fold increase in the release timescale. In a dual-therapeutic composite coating, the top GS component itself was found to be an effective physical barrier for the underlying rhBMP-2, leading to an order of magnitude increase in the release timescale compared to the single-component rhBMP-2 system. The introduction of a laponite interlayer barrier further enhanced the temporal separation between release of the two drugs, resulting in a more physiologically appropriate dosing of rhBMP-2. Both therapeutics released from the composite coating retained their efficacy over their established release timeframes. This new platform for multi-drug localized delivery can be easily fabricated, tuned, and translated to a variety of implant applications where control over spatial and temporal release profiles of multiple drugs is desired.
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影响因子：
14
作者：
Daghighi, Seyedmojtaba;Sjollema, Jelmer;Rochford, Edward T. J.
通讯作者：
Rochford, Edward T. J.
DOI：
10.1016/j.jconrel.2008.07.032
发表时间：
2008-11-12
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Macdonald M;Rodriguez NM;Smith R;Hammond PT
通讯作者：
Hammond PT
影响因子：
19
作者：
Liu, Lei;Grunlan, Jaime C.
通讯作者：
Grunlan, Jaime C.
影响因子：
29.4
作者：
Gaharwar, Akhilesh K.;Mihaila, Silvia M.;Khademhosseini, Ali
通讯作者：
Khademhosseini, Ali
影响因子：
9.7
作者：
Gaharwar, Akhilesh K.;Schexnailder, Patrick J.;Schmidt, Gudrun
通讯作者：
Schmidt, Gudrun