Characterisation of the molecular mechanism of permeation of the Prodrug Me-5ALA across the human Stratum Corneum using molecular dynamics simulations

Janonna Kadyrov; Lanie Ruiz-Perez; Heather A. E. Benson; Ricardo L. Mancera

doi:10.3390/ijms232416001

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Characterisation of the molecular mechanism of permeation of the Prodrug Me-5ALA across the human Stratum Corneum using molecular dynamics simulations

Journal article

Open access

Peer reviewed

Characterisation of the molecular mechanism of permeation of the Prodrug Me-5ALA across the human Stratum Corneum using molecular dynamics simulations

Janonna Kadyrov, Lanie Ruiz-Perez, Heather A. E. Benson and Ricardo L. Mancera

International journal of molecular sciences, Vol.23(24), Art. 16001

2022

DOI: https://doi.org/10.3390/ijms232416001

PMID: 36555643

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Abstract

Biochemistry & Molecular Biology

Chemistry

Chemistry, Multidisciplinary

Life Sciences & Biomedicine

Physical Sciences

Science & Technology

The barrier imposed by the outer layer of the skin, the stratum corneum, creates an almost impermeable environment for exogenous substances. Few lipophilic drugs with low molecular mass can passively diffuse through this layer, highlighting the need to develop methods to enable the delivery of more drugs via the transdermal route. The prodrug approach involves modifying the structure of a drug molecule to enhance its permeability across the skin, but it is often difficult to predict how exactly changes in chemical structure affect permeation. This study uses molecular dynamics simulations to predict permeability values and adequately characterise the molecular mechanism of permeation of the prodrugs Me-5ALA and its parent compound 5ALA across a molecular model of the lipid bilayers of the human stratum corneum. The influence of increased hydrophobicity in Me-5ALA on its permeation revealed a reduction in hydrogen bonding capability that enables it to interact more favourably with the hydrophobic region of the bilayer and diffuse at a faster rate with less resistance, thus making it a better permeant compared to its more hydrophilic parent compound. This molecular simulation approach offers a promising route for the rational design of drug molecules that can permeate effectively across the stratum corneum.

Details

Title: Characterisation of the molecular mechanism of permeation of the Prodrug Me-5ALA across the human Stratum Corneum using molecular dynamics simulations
Authors/Creators: Janonna Kadyrov - Curtin University
Lanie Ruiz-Perez - Curtin University
Heather A. E. Benson - Curtin University
Ricardo L. Mancera - Curtin University
Publication Details: International journal of molecular sciences, Vol.23(24), Art. 16001
Publisher: MDPI
Number of pages: 16
Grant note: Government of Western Australia Australian Government Curtin International Postgraduate Research Scholarship
Identifiers: 991005564669407891
Murdoch Affiliation: Australian National Phenome Centre; Health Futures Institute
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 2 Chemistry; 2.176 Drug Delivery Chemistry; 2.176.771 Transdermal Delivery
Web Of Science research areas: Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
ESI research areas: Chemistry