PMID- 33359754
OWN - NLM
STAT- MEDLINE
DCOM- 20210927
LR  - 20210927
IS  - 1873-3441 (Electronic)
IS  - 0939-6411 (Linking)
VI  - 159
DP  - 2021 Feb
TI  - Dendrimer-mediated permeation enhancement of chlorhexidine digluconate: 
      Determination of in vitro skin permeability and visualisation of dermal 
      distribution.
PG  - 77-87
LID - S0939-6411(20)30373-8 [pii]
LID - 10.1016/j.ejpb.2020.12.014 [doi]
AB  - 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-NH(2)) 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(R), 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-NH(2) 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.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Kirkby, Melissa
AU  - Kirkby M
AD  - School of Pharmacy and Bioengineering, Keele University, Staffordshire ST5 5BG, 
      United Kingdom. Electronic address: m.kirkby@qub.ac.uk.
FAU - Sabri, Akmal B
AU  - Sabri AB
AD  - School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 
      2RD, United Kingdom.
FAU - Scurr, David J
AU  - Scurr DJ
AD  - School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 
      2RD, United Kingdom.
FAU - Moss, Gary P
AU  - Moss GP
AD  - School of Pharmacy and Bioengineering, Keele University, Staffordshire ST5 5BG, 
      United Kingdom.
LA  - eng
PT  - Journal Article
DEP - 20210103
PL  - Netherlands
TA  - Eur J Pharm Biopharm
JT  - European journal of pharmaceutics and biopharmaceutics : official journal of 
      Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
JID - 9109778
RN  - 0 (Anti-Infective Agents, Local)
RN  - 0 (Dendrimers)
RN  - 0 (Drug Carriers)
RN  - 0 (Gels)
RN  - 0 (PAMAM Starburst)
RN  - MOR84MUD8E (chlorhexidine gluconate)
RN  - R4KO0DY52L (Chlorhexidine)
SB  - IM
MH  - Animals
MH  - Anti-Infective Agents, Local/*administration & dosage/pharmacokinetics
MH  - Chlorhexidine/administration & dosage/*analogs & derivatives/pharmacokinetics
MH  - Dendrimers/chemistry/*pharmacology
MH  - Drug Carriers/chemistry/*pharmacology
MH  - Gels
MH  - Models, Animal
MH  - Permeability/drug effects
MH  - Skin/drug effects/*metabolism
MH  - Skin Absorption/drug effects
MH  - Spectrometry, Mass, Secondary Ion
MH  - Swine
MH  - Tissue Distribution
MH  - Water Loss, Insensible/drug effects
OTO - NOTNLM
OT  - Chlorhexidine
OT  - In vitropercutaneous absorption
OT  - PAMAM dendrimer
OT  - Penetration enhancer
OT  - Tape stripping
OT  - Time-of-Flight Secondary Ion Mass Spectrometry
EDAT- 2020/12/29 06:00
MHDA- 2021/09/28 06:00
CRDT- 2020/12/28 10:50
PHST- 2020/07/06 00:00 [received]
PHST- 2020/11/06 00:00 [revised]
PHST- 2020/12/15 00:00 [accepted]
PHST- 2020/12/29 06:00 [pubmed]
PHST- 2021/09/28 06:00 [medline]
PHST- 2020/12/28 10:50 [entrez]
AID - S0939-6411(20)30373-8 [pii]
AID - 10.1016/j.ejpb.2020.12.014 [doi]
PST - ppublish
SO  - Eur J Pharm Biopharm. 2021 Feb;159:77-87. doi: 10.1016/j.ejpb.2020.12.014. Epub 
      2021 Jan 3.