Capsule Integrated Polypeptide Multilayer Films for Effective pH-Responsive Multiple Drug Co-Delivery.

Many applications using drug-carrying biomedical materials require on-demand, localized delivery of multiple therapeutic agents in precisely controlled and patient-specific time sequences, especially after assembly of the delivery vehicles; however, creating such materials has proven extremely challenging. Here we report a novel strategy to create polypeptide multilayer films integrated with capsules as vehicles for co-delivery of multiple drugs using layer-by-layer self-assembly technology. Our approach allows the multilayered polypeptide nanofilms and pre-impregnated capsules to assemble into innovative biomedical materials with high and controllable loading of multiple drugs at any time post-preparation, and to achieve pH-responsive and sustained release. The resulting capsule integrated polypeptide multilayer films effectively co-deliver various drugs with very different properties, including proteins (e.g., growth factors) and nanoparticles, achieving bovine serum albumin loading of 80 μg cm-2 and release of two weeks, and histone loading of 100 μg cm-2 and release of six weeks; which also enable S. aureus killing efficiency of 83% while maintaining osteoblast viability of >85% with silver nanoparticle delivery; and >5-fold cell adhesion and proliferation capability with live cell percentage of >90% via rhBMP-2 delivery. The successful development of such fascinating materials can not only function as advanced nanocoatings to reduce two major complications of orthopedic bone injuries (i.e., infection and delayed bone regeneration), but also provide new insights into the design and development of multifunctional materials for various other biomedical applications.