Antibiotic release from keratin hydrogels for use in wound healing applications

Skin injuries, particularly severe injuries, such as full-thickness wounds or surgical sites, are susceptible to bacterial infection. Materials composed of keratin proteins have been investigated for use in wound dressings, and at least two products based on these materials have received FDA clearance for treating radiation dermatitis via the 510(k) mechanism. We hypothesized that hydrogels composed of oxidatively extracted keratins, known as keratose, could achieve sustained release of several classes of antibiotic drugs that might improve the performance of keratins as wound dressing materials. Reverse-phase high performance liquid chromatography methods were developed to quantify release of ciprofloxacin, cefazolin, and neomycin antibiotics from keratose hydrogels. Nearly 100% of ciprofloxacin and cefazolin were released from the hydrogels within 7 d, while only approximately 20% of neomycin was released. In a combination keratose hydrogel containing neomycin and cefazolin, the amount of cefazolin release decreased (compared to hydrogels with only cefazolin) to about 60% over 7 d whereas neomycin release increased (compared to hydrogels with only neomycin) to nearly 30%. The antibiotics released from the hydrogels inhibited growth of gram-positive (S. aureus) and gram-negative (P. aeruginosa) bacteria in anin vitrobroth inhibition assay. Keratose hydrogels containing a combination of the first-line antibiotics neomycin and cefazolin inhibitedS. aureusfor 18 d andP. aeruginosafor 6 d which was comparable to or better than hydrogels containing broad-spectrum ciprofloxacin that had effect for 11 d. This work suggests that modification of keratin biomaterials with antibiotics may enhance their utility by inhibiting bacterial infections.