title: Interfacial Stacks of Polymeric Nanofilms on Soft Biological Surfaces that Release Multiple Agents.
abstract: We report a general and facile method that permits the transfer (stacking) of multiple independently fabricated and nanoscopically thin polymeric films, each containing a distinct bioactive agent, onto soft biomedically relevant surfaces (e.g., collagen-based wound dressings). By using polyelectrolyte multilayer films (PEMs) formed from poly(allyl amine hydrochloride) and poly(acrylic acid) as representative polymeric nanofilms and micrometer-thick water-soluble poly(vinyl alcohol) sacrificial films to stack the PEMs, we demonstrate that it is possible to create stacked polymeric constructs containing multiple bioactive agents (e.g., antimicrobial and antibiofilm agents) on soft and chemically complex surfaces onto which PEMs cannot be routinely transferred by stamping. We illustrate the characteristics and merits of the approach by fabricating stacks of Ga3+(antibiofilm agent)- and Ag+(antimicrobial agent)-loaded PEMs as prototypical examples of agent-containing PEMs and demonstrate that the stacked PEMs incorporate precise loadings of the agents and provide flexibility in terms of tuning release rates. Specifically, we show that simultaneous release of Ga3+and Ag+from the stacked PEMs on collagen-based wound dressings can lead to synergistic effects on bacteria, killing and dispersing biofilms formed by Pseudomonas aeruginosa (two strains: ATCC 27853 and MPAO1) at sufficiently low loadings of agents such that cytotoxic effects on mammalian cells are avoided. The approach is general (a wide range of bioactive agents other than Ga3+and Ag+can be incorporated into PEMs), and the modular nature of the approach potentially allows end-user functionalization of soft biological surfaces for programmed release of multiple bioactive agents.
authors: Department of Chemical and Biological Engineering, University of Wisconsin-Madison , 1415 Engineering Drive, Madison, Wisconsin 53706, United States.
authors: Maggie
authors: M
authors: Herron
authors: Division of General Surgery, Mountain Area Health Education Center , 509 Biltmore Avenue, Asheville, North Carolina 28801, United States.
authors: Michael J
authors: MJ
authors: Schurr
authors: Department of Ophthalmology and Vision Sciences, School of Medicine and Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis , 1423 Tupper Hall, Davis, California 95616, United States.
authors: Christopher J
authors: CJ
authors: Murphy
authors: Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison , 2015 Linden Drive, Madison, Wisconsin 53706, United States.
authors: Jonathan F
authors: JF
authors: McAnulty
authors: Department of Pathobiology, School of Veterinary Medicine, University of Wisconsin-Madison , 2015 Linden Drive, Madison, Wisconsin 53706, United States.
authors: Charles J
authors: CJ
authors: Czuprynski
authors: Department of Chemical and Biological Engineering, University of Wisconsin-Madison , 1415 Engineering Drive, Madison, Wisconsin 53706, United States.
authors: Nicholas L
authors: NL
authors: Abbott
keywords: biofilms; biomedical surfaces; interfacial constructs; multiple bioactive agents; soft biological interfaces; stacking of polymeric nanofilms; synergistic effects