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 Ga (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 Ga 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 Ga 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.

pH-Responsive Polyelectrolyte Coatings that Enable Catheter-Mediated Transfer of DNA to the Arterial Wall in Short and Clinically Relevant Inflation Times

“…These strategies have generally focused on the design of multilayers that erode, disassemble, or deconstruct in aqueous environments promoted, at least in part, by the chemical degradation of their polymeric building blocks. For example, cationic polymers that are hydrolytically, ,,,,, reductively, − ,, or enzymatically degradable have been used to tune film disassembly and promote the sustained, surface-mediated release of DNA over periods ranging from days to weeks or months. ,,, In contrast, there are fewer reports describing approaches useful for the release or delivery of DNA on shorter time scales (e.g., over periods of a few seconds or a few minutes). ,,− In the context of potential applications in clinical interventions, another significant and related challenge lies in designing PEMs that can be transferred rapidly and faithfully from one surface to a second target surface (e.g., by temporarily pressing a coated device into contact with soft tissue). , Materials that promote the contact transfer of DNA onto other soft surfaces could provide new tools for basic biomedical research and could also enable new approaches to localized gene-based therapies. The degree of control over physicochemical and temporal factors that influence the levels of film stabilityand instabilityrequired for effective contact transfer differs substantially from that required for the design of PEMs that simply disintegrate and release their contents into solution.…”

“…49,54,59−61 In the context of potential applications in clinical interventions, another significant and related challenge lies in designing PEMs that can be transferred rapidly and faithfully from one surface to a second target surface (e.g., by temporarily pressing a coated device into contact with soft tissue). 62,63 Materials that promote the contact transfer of DNA onto other soft surfaces could provide new tools for basic biomedical research and could also enable new approaches to localized gene-based therapies. The degree of control over physicochemical and temporal factors that influence the levels of film stability�and instability�required for effective contact transfer differs substantially from that required for the design of PEMs that simply disintegrate and release their contents into solution.…”

Electrical Field-Assisted Gene Delivery from Polyelectrolyte Multilayers

“…This versatile technique can be utilized for drug delivery because the release of polyelectrolytes depends highly on the structure and composition of polyelectrolyte multilayers (PEMs) [1]. Drug delivery through PEMs give good spatial control; thus, this method can be applied to different medical devices such as stents [2,3], intraocular lens [4], dental implants [5], tissue engineering scaffolds [6,7], wound dressings [8,9], and bone grafts [10,11], by which not only drugs can be locally delivered to the target sites but their therapeutic effects can also be extended through the continuous releases. Nucleotides, such as siRNA and DNA, are especially suitable for controlled delivery through PEMs because these anionic biomacromolecules can be immobilized with polycations easily through LbL assembly [12][13][14][15][16].…”

Polyelectrolyte multilayers for bio‐applications: recent advancements

“…The key feature that makes LbL assembly a preferred choice for bio‐applications is the easy inclusion of biomolecules such as proteins, tissue growth factors, DNA, RNA and so on into the assembly process [12]. Several recent examples demonstrate PEM to be employed as efficient reservoirs for diverse cargo, including multiple bioactive agents [13] such as DNA and gene cargo for the sustained and targeted release [14]. Such excellent loading behaviours of these PEM have also been employed for the advancement of various biomedical applications including the creation of drug eluting stents, delivery of antibiotic and anti‐inflammatory drugs, guided differentiation of stem cells in tissue engineering and transcutaneous surface mediated delivery of vaccines and adjuvants [15].…”