A-Blocks Surgical Hydrogel for Prevention of Infections in Surgery and Trauma
Abstract
This proposal targets the topic area "Healthcare-Acquired Infection Reduction" and addresses the Peer Reviewed Medical Research Program priority for "development of new antimicrobials for the treatment of emerging resistant healthcare-associated infections." The Problem: Our natural defenses against infection involve both antimicrobial activities and physical properties, such as the barrier formed by intact skin. When these defenses are broken by surgery or trauma, both antimicrobial activities and physical properties are lost. To address the problem, both should be replaced until healing occurs. Designed for these settings, A-BLOCKS (Amino Acid Block Copolymers) may provide an answer. Solution to the Problem: The A-BLOCKS SURGICAL HYDROGEL is an innovative product designed to prevent and treat the infections of surgery and trauma. A-BLOCKS provide a unique combination of broad antimicrobial activities and beneficial physical properties. The A-BLOCKS themselves are long-chain (typically over 100 amino acids), positively-charged (cationic) molecules that bind to negatively charged (anionic) molecules on the surface of bacteria. The A-BLOCKS SURGICAL HYDROGEL candidates are active against the Gram-positive and Gram-negative pathogens commonly found in soft tissue-infections of surgery and trauma, including multidrug-resistant bacteria (>99.99% killing). The proposed mechanism of action is similar to that of antimicrobial peptides found throughout nature and should limit development of resistance. Designed for local application, the A-BLOCKS SURGICAL HYDROGEL is a flowable hydrogel that can flow through small openings and rapidly re-gel. It can fill and coat tissues, providing an active and physical antimicrobial barrier. Made from just two amino acids, lysine and leucine, A-BLOCKS are designed to be fully bioresorbable. The Current Proposal: In the proposed studies, we focus on reaching and surpassing late-stage preclinical milestones in the development of the A-BLOCKS SURGICAL HYDROGEL. Specifically, the proposed studies include the validation of key analytical procedures, production of more than 200 grams of clinical-grade material under current Good Manufacturing Practice guidelines, and performance of an essential set of toxicology studies under Good Laboratory Practice guidelines. Successful accomplishment of these tasks should position us well for discussions with the FDA and rapid advancement of the A-BLOCKS SURGICAL HYDROGEL clinical candidate into first-in-patient clinical trials. Impact: Anticipated uses of A-BLOCKS SURGICAL HYDROGEL include prevention of surgical site infections, prophylaxis against infection in contaminated wounds, and treatment of localized infections and abscesses requiring surgical intervention. This product would be an important addition to the military, from battlefield application to use as a part of a dressing for debrided wounds. We believe its physical properties make it ideal for application immediately following wounding. In some patients, simultaneous treatment with systemic antibiotics is envisioned. It is anticipated that the A-BLOCKS SURGICAL HYDROGEL will support better antibiotic stewardship and help prevent the emergence and transmission of antibiotic-resistant bacteria.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610561
Entities
People
- Carl Edwards Iii
Organizations
- Amicrobe (United States)
- United States Army