Microneedle-Mediated Permeation Enhancement of Chlorhexidine Digluconate: Mechanistic Insights Through Imaging Mass Spectrometry

Abstract

Purpose: Chlorhexidine digluconate (CHG) is a first-line antiseptic agent typically applied to the skin as a topical solution prior to surgery due to its efficacy and safety profile. However, the physiochemical properties of CHG limits its cutaneous permeation, preventing it from reaching potentially pathogenic bacteria residing within deeper skin layers. Thus, the utility of a solid oscillating microneedle system, Dermapen®, and a CHG-hydroxyethylcellulose (HEC) gel were investigated to improve the intradermal delivery of CHG. Methods: Permeation of CHG from the commercial product, Hibiscrub®, and HEC-CHG gels (containing 1% or 4% CHG w/w) was assessed in intact skin, or skin that had been pre-treated with microneedles of different array numbers, using an Franz diffusion cells and Time-of-Flight Secondary Ion Mass Spectrometry (ToF–SIMS). Results: Gels containing 1% and 4% CHG resulted in significantly increased depth permeation of CHG compared to Hibiscrub® (4% w/v CHG) when applied to microneedle pre-treated skin, with the effect being more significant with the higher array number. ToF–SIMS analysis indicated that the depth of dermal penetration achieved was sufficient to reach the skin strata that typically harbours pathogenic bacteria, which is currently inaccessible by Hibiscrub®, and showed potential lateral diffusion within the viable epidermis. Conclusions: This study indicates that HEC-CHG gels applied to microneedle pre-treated skin may be a viable strategy to improve the permeation CHG into the skin. Such enhanced intradermal delivery may be of significant clinical utility for improved skin antisepsis in those at risk of a skin or soft tissue infection following surgical intervention.