Characterization of the in vitro, ex vivo, and in vivo Efficacy of the Antimicrobial Peptide DPK-060 Used for Topical Treatment

Abstract

Antimicrobial peptides, also known as host defense peptides, have recently emerged as a promising new category of therapeutic agents for the treatment of infectious diseases. This study evaluated the preclinical in vitro, ex vivo , and in vivo antimicrobial activity, as well as the potential to cause skin irritation, of human kininogen-derived antimicrobial peptide DPK-060 in different formulations designed for topical delivery. We found that DPK-060 formulated in acetate buffer or poloxamer gel caused a marked reduction of bacterial counts of Staphylococcus aureus in vitro (minimum microbicidal concentration <5 μg/ml). We also found that DPK-060 in poloxamer gel significantly suppressed microbial survival in an ex vivo wound infection model using pig skin and in an in vivo mouse model of surgical site infection (≥99 or ≥94% reduction in bacterial counts was achieved with 1% DPK-060 at 4 h post-treatment, respectively). Encapsulation of DPK-060 in different types of lipid nanocapsules or cubosomes did not improve the bactericidal potential of the peptide under the applied test conditions. No reduction in cell viability was observed in response to administration of DPK-060 in any of the formulations tested. In conclusion, the present study confirms that DPK-060 has the potential to be an effective and safe drug candidate for the topical treatment of microbial infections; however, adsorption of the peptide to nanocarriers failed to show any additional benefits.

An Update on Antimicrobial Peptides (AMPs) and Their Delivery Strategies for Wound Infections

“…Very surprisingly, Håkansson et al loaded DPK-060 into three different nanosystems: lipid nanocapsules (LNCs), nanocubes, and polaxamer gels compared to the parent DPK-060 peptide in acetate buffer. No enhanced effect was found when encapsulating DPK-060 in any of the formulations, except when including AMP in polaxamer gels [199]. This points out the need for a specific optimization of the carrier for a given peptide through activity and toxicity testing.…”

An Update on Antimicrobial Peptides (AMPs) and Their Delivery Strategies for Wound Infections

“…The results showed that RADA16 peptide hydrogels were able to release active TGF-β1 growth factor and significantly influenced the proliferation of stem cells [168]. including AMP in polaxamer gels [169]. This point out the need for a specific optimization of the carrier for a given peptide, through thorough activity and toxicity testing.…”

Antimicrobial peptides as therapeutic agents: opportunities and challenges

“…Pexiganan has been evaluated as a topical cream in two phase III clinical trials for the treatment of mild infections in diabetic foot ulcers (NCT01590758, NCT01594762) and additional clinical studies are reportedly planned in cSSSI including surgical wounds, burns, and decubitus ulcers [69]. Similarly to omiganan and pexiganan, DPK-060 (structurally derived from human protein kininogen) also displays a broad spectrum of antimicrobial actions [70][71][72]. The efficacy of DPK-060 ointment has been studied in clinical phase II trials in the treatment of infections in atopic dermatitis (NCT01522391) [72] and acute external otitis (NCT01447017).…”