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

• Published in: Pharmaceutical research Vol. 39; no. 8; pp. 1945 - 1958
• Main Authors: Kirkby, Melissa, Sabri, Akmal Bin, Scurr, David, Moss, Gary
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2022; Springer; Springer Nature B.V
• Subjects: Anti-Infective Agents, Local - pharmacology; Backup software; Bacteria; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Chlorhexidine; Chlorhexidine - analogs & derivatives; Chlorhexidine - pharmacology; Epidermis; Gels; Gels - pharmacology; Health aspects; Ions; Lateral diffusion; Mass Spectrometry; Mass spectroscopy; Medical Law; Original; Original Research Article; Pharmacology/Toxicology; Pharmacy; Safety regulations; Scientific imaging; Skin; Skin care products; microneedles; skin permeation; skin Imaging; chlorhexedine; time of flight secondary ion mass spectrometry
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-022-03309-8

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.