Hsu Bryan B, Jamieson Kelsey S, Hagerman Samantha R, Holler Eggehard, Ljubimova Julia Y, Hammond Paula T
Koch Institute for Integrative Cancer Research and the Institute for Soldier Nanotechnologies, Massachusetts Institute for Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 (USA); Department of Chemistry, Massachusetts Institute for Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 (USA).
Angew Chem Int Ed Engl. 2014 Jul 28;53(31):8093-8. doi: 10.1002/anie.201403702. Epub 2014 Jun 18.
Multidrug regimens can sometimes treat recalcitrant diseases when single-drug therapies fail. Recapitulating complex multidrug administration from controlled release films for localized delivery remains challenging because their release kinetics are frequently intertwined, and an initial burst release of each drug is usually uncontrollable. Kinetic control over protein release is demonstrated by cross-linking layer-by-layer films during the assembly process. We used biodegradable and naturally derived components and relied on copper-free click chemistry for bioorthogonal covalent cross-links throughout the film that entrap but do not modify the embedded protein. We found that this strategy restricted the interdiffusion of protein while maintaining its activity. By depositing a barrier layer and a second protein-containing layer atop this construct, we generated well-defined sequential protein release with minimal overlap that follows their spatial distribution within the film.
当单一药物疗法失败时，多药方案有时可以治疗顽固性疾病。从控释膜进行局部给药来重现复杂的多药给药仍然具有挑战性，因为它们的释放动力学常常相互交织，而且每种药物的初始突释通常是无法控制的。在组装过程中通过交联层层膜证明了对蛋白质释放的动力学控制。我们使用了可生物降解的天然衍生成分，并依靠无铜点击化学在整个膜中形成生物正交共价交联，这种交联捕获但不修饰嵌入的蛋白质。我们发现这种策略在保持蛋白质活性的同时限制了其相互扩散。通过在该构建体上沉积一个阻挡层和第二个含蛋白质层，我们产生了定义明确的顺序蛋白质释放，其重叠最小，且遵循它们在膜内的空间分布。
