Poster No. 4
Title:
Silk Biomaterials for Enhanced Stability and Controlled Release of Antibiotics
Authors:
Eleanor Pritchard, Thomas Valentin, Fiorenzo G. Omenetto, David Kaplan
Presented by:
Eleanor Pritchard
Department:
Department of Biomedical Engineering, Tufts University School of Engineering
Abstract:
Typical systemic delivery of antibiotics can be limited by difficulty of penetrating epithelial barrier shells around infections and the risk of liver damage with large doses. In addition, antibiotic instability at temperatures
≥25 o C makes transport and storage difficult (particularly in third world clinical settings where refrigeration is limited). A simple system for antibiotic delivery is needed that also stabilizes the incorporated drug, biodegrades to avoid surgical retrieval, and restricts delivery to a specific target site to minimize side-effects and maximize efficacy of dose. This need demands a novel approach to the storage and delivery of antibiotics. Silk, a naturally derived protein polymeric biomaterial, is biocompatible, safe, FDA approved and degrades in vivo to nontoxic products. Further, the unique protein chemistry composition of silk has proven useful for the stabilization of antibiotics as well as other drugs. Antibiotic-loaded silk biomaterials (including films, sponges, gels and microspheres) could be stored for extended periods at room temperature then injected, applied directly to wound sites, or the antibiotic liberated via protease treatment. These materials could deliver antibiotics locally
(avoiding systemic side effects) and then degrade naturally over time.
Release of antibiotics from silk films, gels, microspheres and combinations was examined using a bacterial lawn
( Staphylococcus aureus , Gram Positive, and Escherichia coli, Gram Negative bacteria) based on zone of inhibition. Long term stability was assessed to compare penicillin stored in solution versus stored in silk films at
4 o C (refrigeration), 25 o C (room temperature) and 37 o C (body temperature). Hydrogels loaded with penicillin or ampicillin sustained release for 48 hours and 4 days, respectively. Penicillin and ampicillin loaded silk microspheres suspended in silk gels released a lower daily rate than bulk loaded gels but continued to release for
4-5 days. Penicillin stability declined rapidly when stored in solution, but penicillin stored in silk films retained activity above 60% for 19 days at all storage temperatures. Over 80% of the original penicillin activity was detected after 12 days of storage in silk films at 37 o C (compared to less than 5% for penicillin in solution).
Silk biomaterials are capable of sustained antibiotic release and could be used to deliver both large initial clearance doses and slower sustained maintenance doses depending on mode of processing. Incorporation of
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Poster No. 4 penicillin into silk films substantially enhances stability compared to storage in solution, preserving significant activity even when stored at room temperature and body temperature. We conclude that antibiotics
(including penicillin) can be stored in silk biomaterials (at temperatures as high as 37 o C) and the drug can be effectively released with bioactivity. These silk-based antibiotic storage and delivery systems would be especially useful in third world clinical settings due to the elimination of the need for refrigeration, ease of transport and storage, and the ability to efficiently release antibiotics locally over sustained timeframes without constant reapplication, multiple repeated injections or a need for surgical retrieval.
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