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 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.

pH-controlled delivery of gentamicin sulfate from orthopedic devices preventing nosocomial infections

“…Numerous drug delivery systems (DDS) of antibiotic are presented in the literature [48][49][50]. The ideal DDS for the bacterial infection is described as having the following characteristics [51]: it must have a wide spectrum activity (efficient against the most common bacterial pathogens involved in chronic osteomyelitis); it must be locally released; it must be unable to enter in the systemic circulation; it must be stable at the body temperature; it must not produce supra infection.…”

Small-molecule-hosting nanocomposite films with multiple bacteria-triggered responses

“…Therefore, new multifunctional coatings are being explored that combine releasekilling and contact-killing capabilities. 23,24 Moreover, antibacterial surfaces have been designed that can respond to light or pH. 25,26 The present study goes beyond this prior work by describing a new type of coating that was engineered to combine permanent, contactkilling protection with bacteria-triggered, on-demand release of antimicrobials.…”

Dual Action Antimicrobials: Nitric Oxide Release from Quaternary Ammonium-Functionalized Silica Nanoparticles

“…18 Although these releasable therapies are potent antimicrobials, resistance concerns plaque their wide-spread use. 46, 47 The QA-functionalized particles described herein were designed to allow for the release of NO, a broad-spectrum antimicrobial with low risk of resistance.…”

“…7, 17 Similarly, Wong et al reported improved efficacy of QA-functionalized layer-by-layer coatings that leached gentamicin against biofilm formation. 18 …”