Enhanced topical antimicrobial delivery for improved skin antisepsis

The National Institute for Health and Care Excellence recommend the routine use of topically applied chlorhexidine digluconate (CHX) formulations to eliminate skin microorganisms prior to incision to prevent surgical site infections (SSI). However, CHX exhibits poor permeation through the stratum corneum and consequently is not effective in eliminating all skin microbes, resulting in an increased chance of patients acquiring infection. This study validates an in vitro porcine permeation model (Franz-type diffusion cell) by comparing CHX permeation through the porcine stratum corneum to in vivo human stratum corneum. Tape strips were sampled from the epidermis of both models and CHX distribution and abundance was analysed using time-of-flight secondary ion mass spectrometry (ToF-SIMS) and high performance liquid chromatography (HPLC). Once validated, the in vitro porcine model was used to determine the CHX permeation enhancement abilities of a series of experimental compounds, including R6 polyarginine, glycolic acid and Kolliphor® HS15. The porcine stratum corneum was tape stripped following treatment with these compounds and ToF-SIMS and HPLC was used to analyse permeation enhancement. This research demonstrated the similarity in CHX permeation through in vivo human skin and the in vitro porcine skin permeation model. Using the porcine model, we determined that R6 polyarginine, glycolic acid and Kolliphor® HS15 significantly increased CHX delivery through the entire epidermis. Finally, we demonstrate that our permeation enhancer formulations improve skin antisepsis throughout the stratum corneum whilst causing no additional cytotoxicity to mammalian cells compared to clinical formulations. This research highlights three potential novel CHX formulation strategies for reducing SSI occurrence.