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Kirkby, M, Sabri, AB, Scurr, DJ and Moss, GPJ (2021) Dendrimer-mediated permeation enhancement of chlorhexidine digluconate: Determination of in vitro skin permeability and visualisation of dermal distribution. European Journal of Pharmaceutics and Biopharmaceutics, 159. 77 - 87. ISSN 0939-6411
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Abstract
Chlorhexidine digluconate (CHG) is a cationic bisbiguanide used in the UK as the first-line skin antiseptic prior to surgery in the UK due to its favourable efficacy and safety profile, high affinity for skin binding and minimal reports of resistance. Despite this, bacteria remain within deeper skin layers, furrows and appendages that are considered inaccessible to CHG, due to its poor dermal penetration. In this study a third generation, polyamidoamine dendrimer (G3 PAMAM-NH2) was utilised to improve dermal penetration of CHG. A topical gel formulation was optimised to maximise CHG delivery (containing 0.5% gelling agent and 4% drug), followed by drug and dendrimer co-formulation into a commercially viable gel. The gel containing 4% CHG and 1 mM PAMAM dendrimer significantly increased the depth permeation of CHG compared to the commercial benchmark (Hibiscrub®, containing 4% w/v CHG) (p < 0.05). The optimised formulation was further characterised using Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS), which 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 commercial CHG formulations. This study therefore indicates that a G3 PAMAM-NH2 dendrimer gel may be viable as a permeation enhancer of CHG, for improved skin antisepsis in those at risk of a skin or soft tissue infection as a result of surgical intervention.
Item Type: | Article |
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Additional Information: | The final version of this accepted article and all relevant information can be found online at; https://www.sciencedirect.com/science/article/pii/S0939641120303738?via%3Dihub |
Uncontrolled Keywords: | PAMAM dendrimer; Time-of-Flight Secondary Ion Mass Spectrometry; Chlorhexidine; In vitro percutaneous absorption; Tape stripping; Penetration enhancer |
Subjects: | R Medicine > RD Surgery R Medicine > RD Surgery > RD32 Operative surgery. Technique of surgical operations R Medicine > RD Surgery > RD98 Surgical complications |
Divisions: | Faculty of Medicine and Health Sciences > School of Pharmacy and Bioengineering |
Depositing User: | Symplectic |
Date Deposited: | 05 Feb 2021 09:19 |
Last Modified: | 03 Jan 2022 01:30 |
URI: | https://eprints.keele.ac.uk/id/eprint/9131 |