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Dual functional polyelectrolyte multilayer coatings for implants: permanent microbicidal base with controlled release of therapeutic agents.

ABSTRACT: 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.

SUBMITTER: Wong SY

PROVIDER: S-EPMC3218101 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Dual functional polyelectrolyte multilayer coatings for implants: permanent microbicidal base with controlled release of therapeutic agents.

Wong Sze Yinn SY Moskowitz Joshua S JS Veselinovic Jovana J Rosario Ryan A RA Timachova Ksenia K Blaisse Michael R MR Fuller Renée C RC Klibanov Alexander M AM Hammond Paula T PT

Journal of the American Chemical Society 20101124 50

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 inflamm ...[more]

PMID: 21105659

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Project description:The field of membranes saw huge developments in the last decades with the introduction of both polyelectrolyte multilayer (PEM)-based membranes and biomimetic membranes. In this work, we combine these two promising systems and demonstrate that proteopolymersomes (PP+) with the incorporated aquaporin protein can be distributed in a controlled fashion using PEMs, even on the inner surface of a hollow fiber membrane. In this way, various proteopolymersome multilayers (PPMs) are fabricated using PP+ as the positively charged species in combination with the polyanions poly(styrene 4-sulfonate) (PSS) and poly(acrylic acid) (PAA). It is shown by reflectometry through alternately adsorbing the polyanions and PP+ that, for both PAA and PSS, a good layer growth is possible. However, when the multilayers are imaged by SEM, the PAA-based PPMs show dewetting, whereas vesicular structures can only be clearly observed in and on the PSS-based PPMs. In addition, membrane permeability decreases upon coating the PPMs to 2.6 L?m-2?h-1?bar-1 for PAA/PP+ and 7.7 L?m-2?h-1?bar-1 for PSS/PP+. Salt retentions show that PAA/PP+ layers are defective (salt retentions <10% and high molecular weight cut-off (MWCO)), in line with the observed dewetting behavior, while PPMs based on PSS show 80% MgSO4 retention in combination with a low MWCO. The PSS/PP+ membranes show a Donnan-exclusion behavior with moderate MgCl2 retention (50%-55%) and high Na2SO4 retention (85%-90%) indicating a high amount of negative charge present within the PPMs. The corresponding PEMs, on the other hand, are predominately positively charged with MgCl2 retention of 97%-98% and Na2SO4 retention of 57%-80%. This means that the charge inside the multilayer and, thus, its separation behavior can be changed when PP+ is used instead of a polycation. When comparing the PPM membranes to the literature, similar performances are observed with other biomimetic membranes that are not based on interfacial polymerization, but these are the only ones prepared using a desired hollow fiber geometry. Combining PEMs and biomimetic approaches can, thus, lead to relevant membranes, especially adding to the versatility of both systems.

Dataset Information

Dual functional polyelectrolyte multilayer coatings for implants: permanent microbicidal base with controlled release of therapeutic agents.

Publications

Dual functional polyelectrolyte multilayer coatings for implants: permanent microbicidal base with controlled release of therapeutic agents.

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