Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Breaching the skin barrier - Insights from molecular simulation of model membranes
AU - Notman, Rebecca
AU - Anwar, Jamshed
N1 - Copyright © 2012 Elsevier B.V. All rights reserved.
PY - 2013/2
Y1 - 2013/2
N2 - Breaching the skin's barrier function by design is an important strategy for delivering drugs and vaccines to the body. However, while there are many proposed approaches for reversibly breaching the skin barrier, our understanding of the molecular processes involved is still rudimentary. Molecular simulation offers an unprecedented molecular-level resolution with an ability to reproduce molecular and bulk level properties. We review the basis of the molecular simulation methodology and give applications of relevance to the skin lipid barrier, focusing on permeation of molecules and chemical approaches for breaching the lipid barrier by design. The bulk kinetic model based on Fick's Law describing absorption of a drug through skin has been reconciled with statistical mechanical quantities such as the local excess chemical potential and local diffusion coefficient within the membrane structure. Applications of molecular simulation reviewed include investigations of the structure and dynamics of simple models of skin lipids, calculation of the permeability of molecules in simple model membranes, and mechanisms of action of the penetration enhancers, DMSO, ethanol and oleic acid. The studies reviewed illustrate the power and potential of molecular simulation to yield important physical insights, inform and rationalize experimental studies, and to predict structural changes, and kinetic and thermodynamic quantities.
AB - Breaching the skin's barrier function by design is an important strategy for delivering drugs and vaccines to the body. However, while there are many proposed approaches for reversibly breaching the skin barrier, our understanding of the molecular processes involved is still rudimentary. Molecular simulation offers an unprecedented molecular-level resolution with an ability to reproduce molecular and bulk level properties. We review the basis of the molecular simulation methodology and give applications of relevance to the skin lipid barrier, focusing on permeation of molecules and chemical approaches for breaching the lipid barrier by design. The bulk kinetic model based on Fick's Law describing absorption of a drug through skin has been reconciled with statistical mechanical quantities such as the local excess chemical potential and local diffusion coefficient within the membrane structure. Applications of molecular simulation reviewed include investigations of the structure and dynamics of simple models of skin lipids, calculation of the permeability of molecules in simple model membranes, and mechanisms of action of the penetration enhancers, DMSO, ethanol and oleic acid. The studies reviewed illustrate the power and potential of molecular simulation to yield important physical insights, inform and rationalize experimental studies, and to predict structural changes, and kinetic and thermodynamic quantities.
KW - Transdermal drug delivery
KW - Percutaneous penetration
KW - Skin lipids
KW - Model membrane
KW - Ceramides
KW - Lipid bilayers
KW - Computer modeling
KW - Molecular dynamics simulation
U2 - 10.1016/j.addr.2012.02.011
DO - 10.1016/j.addr.2012.02.011
M3 - Journal article
C2 - 22414344
VL - 65
SP - 237
EP - 250
JO - Advanced Drug Delivery Reviews
JF - Advanced Drug Delivery Reviews
IS - 2
ER -