Medical device related infections are a significant and growing source of morbidity and mortality. Biofilm formation is a common feature of medical device infections that is not effectively prevented or treated by systemic antibiotics. Antimicrobial medical device combination products provide a pathway for local delivery of antimicrobial therapeutics with the ability to achieve high local concentrations while minimizing systemic side effects. In this review, we present considerations for the design of local antimicrobial delivery systems, which can be facilitated by modeling local pharmacokinetics in the context of the target device application. In addition to the need for local delivery, a critical barrier to progress in the field is the need to incorporate agents effective against biofilm. This article aims to review key properties of antimicrobial peptides that make them well suited to meet the demands of the next generation of antimicrobial medical devices, including broad spectrum activity, rapid and biocidal mechanisms of action, and efficacy against biofilm.

BACKGROUND: Stringent requirements must be satisfied by biomedical adhesives, including biocompatibility, adhesion, cohesiveness and processability. The ability to change mechanical properties in response to environmental changes may also be desirable. In the present work the water‐absorbing, adhesive and mechanical properties of blends based on hydrogen bonding complexes between poly(N‐vinyl pyrrolidone), poly(ethylene glycol) (PEG) and poly[(methacrylic acid)‐co‐(ethyl acrylate)] were investigated. These blends, consisting of pharmaceutical‐grade components, exhibit pH‐sensitive swelling and dissolution, along with rubber‐like elasticity and bioadhesion. RESULTS: Polymer blend films remained intact at pH = 5.6 but underwent dissolution at pH = 7.4, the difference being attributed to deprotonation of acidic side‐chains, with loss of hydrogen bonding and development of charge repulsion. Sol release was primarily due to PEG. Films swelled at low pH instead of dissolving, in a manner that was pH‐dependent but PEG‐independent. Films displayed elastic properties comparable to cured elastomers when mildly swollen, with modulus and ultimate strength decreasing with increasing PEG content. Dry films were nearly tack‐free, but became more adhesive with increasing water content, up to a point where the film dissolved. CONCLUSION: Due to their biocompatibility and dissolution/mechanical properties, the bioadhesive polymer blends investigated may be suitable for numerous biomedical applications. Copyright © 2008 Society of Chemical Industry

Wound infections are a common complication of combat-related injuries that significantly increase morbidity and mortality. Multi-drug resistant (MDR) organisms and their associated biofilms play a significant role in the pathogenicity and chronicity of wound infections. A critical barrier to progress in the treatment of traumatic wounds is the need for broad spectrum antimicrobials that are effective against biofilms and compatible with topical delivery. In this study, we present the in vitro efficacy of two de novo designed cationic, antimicrobial peptides and related topical formulations against single species and polymicrobial biofilms of MDR bacteria. Minimum biofilm eradication concentrations for peptides ranged from 0.7 μM for Staphylococcus aureus to 13.2 μM for Pseudomonas aeruginosa. Varying pH did not adversely impact peptide activity, however, in the presence of albumin, minimum biofilm eradication concentrations generally increased. When formulated into gels or dressings, both peptides eradicated mono- and polymicrobial biofilms of MDR pathogens. The biocompatibility index (BI) was found to be greater than one for both ASP-1 and ASP-2, with a slightly greater (more favorable) BI for ASP-2. The BIs for both peptides were greater than BIs previously reported for commonly used topical antimicrobial agents. The antimicrobial peptides and related formulations presented provide a promising platform for treatment of wound biofilms to improve outcomes for those injured in combat.

Introduction Infection frequently complicates the treatment of combat-related wounds, impairs healing, and leads to worse outcomes. To better manage wound infections, antimicrobial therapies that are effective against biofilm and designed for direct wound application are needed. The primary objective of this work was to evaluate a chitosan matrix for delivery of two engineered antimicrobial peptides, (ASP)-1 and ASP-2, to treat biofilm-associated bacteria. A secondary objective was to determine whether replacing the levorotatory (L) form amino acids in ASP-2 with dextrorotatory (D) form amino acids would impact peptide activity. Materials and Methods Chitosan gels loaded with antimicrobial peptides were evaluated for peptide release over 7 days and tested for efficacy against biofilms grown both in vitro on polymer mesh and ex vivo on porcine skin. Results When delivered via chitosan, 70% to 80% of peptides were released over 7 days. Gels eradicated biofilms of gram-positive and gram-negative, drug-resistant bacteria in vitro and ex vivo. Under the conditions tested, no meaningful differences in peptide activity between the L and D forms of ASP-2 were detected. Conclusions Chitosan serves as an effective delivery platform for ASP-1 and ASP-2 to treat biofilm-embedded bacteria and warrants further development as a topical treatment.