1623. Unique Physical Properties of Synthetic Antimicrobial Block Copolypeptides Designed for Wound Infections
Session: Poster Abstract Session: Novel Antimicrobial Agents
Saturday, October 20, 2012
Room: SDCC Poster Hall F-H
Background: Local bacterial and fungal infections present unique biophysical challenges related to altered tissue architecture and function, as well as microbial growth patterns and biofilm formation. We have synthesized long chain, cationic, amphiphilic lysine/leucine block copolypeptides that are broadly antimicrobial. Here we attempt to optimize the biophysical properties of these synthetic block copolypeptides for the prevention and treatment of wound infections. In particular, they are designed for: i) controlled self-assembly into complex hierarchical structures to yield micelle based solutions and hydrogels; ii) enhanced bioadhesiveness for tissue binding; and strong surfactant activity for improved wound cleansing / debridment.

Methods: Interfacial tension and texture analysis were performed using a TX.XT2 Texture Analyzer. A 3 % (w/w) copolypeptide solution was added to a 5 mL plastic vial. A cylindrical stainless steel probe (diameter = 0.25 in.) was attached to the TX.XT2 with a 100 g load cell. The probe was lowered into the copolypeptide solution at 2 mm/s and data captured at 20 pt/s. The maximum force applied to the probe was determined to represent the Firmness of the solution expressed in mN. 

Results: Characterization of two block copolypeptides of identical size and composition, but distinct hydrophobic domain order (based on enantiopurity) demonstrated substantial biophysical differences. First, the block copolypeptide with disordered hydrophobe formed micelle solutions, while the one containing an a-helical hydrophobe formed hydrogels. Second, disordered hydrophobic domain resulted in lower interfacial tension (19 dynes/cm vs. 35 dynes/cm, respectively). In separate studies, block copolypeptides were shown to be mucoadhesive with higher values for the hydrogel forming structures. These biophysical designed features should enable optimization for the prevention and treatment of wound and tissue infections. 

Conclusion:  We have created potent antimicrobial block copolypeptides that self-assemble into a variety of hierarchical structures (e.g. micelles and hydrogels). Our biomaterials provide a biodegradable, protective barrier that could dramatically reduce wound infections.

Jarrod Hanson, Ph.D., Ekaterina Tkatchouk, Ph.D., Evan Schauer, M.S., Kevin Ogilby, B.S., Janet Chow, Ph.D., Diego Benitez, Ph.D. and Michael Bevilacqua, M.D., Ph.D., Amicrobe, Inc., Pasadena, CA

Disclosures:

J. Hanson, Amicrobe, Inc.: Employee, Salary

E. Tkatchouk, Amicrobe, Inc.: Consultant, Consulting fee

E. Schauer, Amicrobe, Inc.: Employee, Salary

K. Ogilby, Amicrobe, Inc.: Employee, Salary

J. Chow, Amicrobe, Inc.: Employee, Salary

D. Benitez, Amicrobe, Inc.: Employee, Salary

M. Bevilacqua, Amicrobe, Inc.: Employee, Salary

Findings in the abstracts are embargoed until 12:01 a.m. PST, Oct. 17th with the exception of research findings presented at the IDWeek press conferences.