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Multilayered Films Fabricated from Plasmid DNA and a Side-Chain Functionalized Poly(-amino Ester): Surface-Type Erosion and Sequential Release of Multiple Plasmid Constructs from Surfaces
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文摘
Hydrolytically degradable polyamines can be used to fabricate multilayered polyelectrolyte films that erode andrelease DNA in aqueous environments. Past studies have investigated films fabricated from poly(-amino ester) 1and the influence of polymer backbone structure on film erosion and the release of anionic polyelectrolytes. Thisinvestigation sought to characterize the influence of polymer side-chain structure on the stability of multilayered filmsin physiologically relevant media. Here, we report on the fabrication and characterization of multilayered films ~150nm thick assembled from plasmid DNA and side-chain functionalized polymer 2. We observed large differences inthe behavior of films fabricated from polymer 2 as compared to films fabricated from polymer 1. Whereas filmsfabricated from polymer 1 erode and release DNA over ~2 days when incubated in phosphate-buffered saline, filmsfabricated from polymer 2 erode and release DNA over ~2 weeks. In addition, whereas films fabricated from polymer1 undergo complex nanometer-scale physical transformations in aqueous media, characterization of the surfaces offilms fabricated from polymer 2 by atomic force microscopy (AFM) demonstrates that the surfaces of these materialsremain smooth and uniform during erosion. The apparent surface-type erosion of these materials permits the fabricationof ultrathin films with architectures that provide control over the timing and the order in which two different DNAconstructs are released from surfaces. For example, the order in which two different DNA constructs are released fromfilms and expressed by cells can be controlled to measurable extents by the relative order in which they are depositedduring fabrication. These results suggest approaches to the localized and sequential release of multiple different DNAconstructs to cells or tissues from the surfaces of tissue engineering scaffolds or implantable devices coated withmultilayered films.

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