Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
J Am Chem Soc. 2010 Dec 22;132(50):17840-8. doi: 10.1021/ja106288c. Epub 2010 Nov 24.
Here we present a new bifunctional layer-by-layer (LbL) construct made by combining a permanent microbicidal polyelectrolyte multilayered (PEM) base film with a hydrolytically degradable PEM top film that offers controlled and localized delivery of therapeutics. Two degradable film architectures are presented: (1) bolus release of an antibiotic (gentamicin) to eradicate initial infection at the implant site, or (2) sustained delivery of an anti-inflammatory drug (diclofenac) to cope with inflammation at the site of implantation due to tissue injury. Each degradable film was built on top of a permanent base film that imparts the implantable device surface with microbicidal functionality that prevents the formation of biofilms. Controlled-delivery of gentamicin was demonstrated over hours and that of diclofenac over days. Both drugs retained their efficacy upon release. The permanent microbicidal base film was biocompatible with A549 epithelial cancer cells and MC3T3-E1 osteoprogenitor cells, while also preventing bacteria attachment from turbid media for the entire duration of the two weeks studied. The microbicidal base film retains its functionality after the biodegradable films have completely degraded. The versatility of these PEM films and their ability to prevent biofilm formation make them attractive as coatings for implantable devices.
我们在此提出了一种新的双层(LbL)结构,它结合了永久性杀菌聚电解质多层(PEM)基底膜和可水解降解的 PEM 顶层膜,可提供治疗药物的控制和局部输送。提出了两种可降解膜结构:(1)抗生素(庆大霉素)的突释,以消除植入部位的初始感染,或(2)抗炎药物(双氯芬酸)的持续释放,以应对由于组织损伤引起的植入部位的炎症。每个可降解膜都构建在永久性基底膜的顶部,赋予可植入装置表面杀菌功能,防止生物膜的形成。庆大霉素的控制释放可在数小时内进行,双氯芬酸的控制释放可在数天内进行。两种药物在释放后仍保持其功效。永久性杀菌基底膜与 A549 上皮癌细胞和 MC3T3-E1 成骨前体细胞具有生物相容性,同时在研究的两周内,还能防止浑浊介质中的细菌附着。在可生物降解膜完全降解后,杀菌基底膜仍保留其功能。这些 PEM 膜的多功能性及其防止生物膜形成的能力使其成为有吸引力的可植入装置涂层。