Preformulation studies on novel garvicin KS peptides for topical applications

Abstract

Antimicrobial peptides (AMPs) are emerging as a viable alternative to antibiotics attributable to their potent antimicrobial effects and low propensity for resistance development, especially in chronic infected wounds. The development of an optimized topical formulation of AMPs is thus warranted. Preformulation studies for determination of the suitability and optimization requirements of AMPs in topical formulation development are important. Therefore, we sought to investigate the preformulation studies for a novel bacteriocin garvicin KS (GarKS), which is composed of three peptides (GakA, GakB, and GakC). The effects of physiological fluids and varying temperatures on GarKS peptide stability were determined. The antimicrobial effects of the peptides and their combinations were evaluated in Staphylococcus aureus (methicillin sensitive and resistant strains). Furthermore, their effects on fibroblast viability and proliferation were determined. The GarKS peptides were stable in water and PBS at room and physiological temperatures, however, the peptides were significantly degraded in simulated wound fluid. The antimicrobial and fibroblast cell viability/proliferation effects of either individual GarKS peptides or their combinations varied. A careful consideration of the peptide stability, antimicrobial efficacy, and fibroblast viability/proliferation effects suggests GakA+GakB as a potent combination for the development of an optimized topical formulation of GarKS peptides.

Keywords: Antimicrobial peptide; Infected wounds; Preformulation; Stability; Topical formulation.