In Silico Studies of Diclofenac Interactions with the Skin Barrier Heriot-Watt University in United Kingdom

To engage its biological target, and provide its analgesic efficacy, topically applied diclofenac must first permeate across the skin’s external barrier, the stratum corneum (SC). The stratum corneum is composed of corneocytes (dead skin cells) surrounded by a dense lipid matrix that serves as the only continuous path for permeation through the skin. The passive permeation of diclofenac across the SC is known to vary greatly depending on the delivery vehicle (formulation) and the diclofenac counter ion. Whilst standard mass balance delivery measurements provide quantitative information on the amount of diclofenac delivered across the skin, and the amount retained within the tissue, such measurements provide no information on the molecular interactions occurring between diclofenac and the composite lamellar lipid structure of the SC. Interestingly, studies have suggested that diclofenac “reservoirs” of different size form within the SC. Their existence and size are important for the long-lasting effect of topical diclofenac. To aid the rational design of superior topical diclofenac formulations a detailed understanding of the molecular interactions between diclofenac, the formulation excipients, and the lipid classes and phases of the SC is needed. In silico simulations offer the potential to provide new understanding that addresses these questions.Over the last decade the McCabe group has developed in silico simulation approaches to study the lipids of the stratum corneum, their structure and molecular interactions. Molecular simulation provides a means to probe the behaviour of stratum corneum lipid systems at length-scales not accessible to experiment and to develop a molecular level understanding of the membrane behaviour.This project will involve performing atomistic molecular dynamics simulations of SC lipid systems to determine some of the critical molecular interactions between diclofenac and the lipid components of the stratum corneum. The output of the simulation studies will be compared with published skin permeation data for different diclofenac salts, ion pairs, and solvent. While Ppior experience with molecular simulations is not required but advantageous, applicants should have some experience in writing computer codes (such as Python or MATLAB).For further information please contact Clare McCabe [email protected] Closing Date: November 23rd 2024. All successful candidates must commence studies no later than January 1.How to ApplyApply OnlineWhen applying through the Heriot-Watt on-line system please ensure you provide the following information:(a) in ‘Study Option’You will need to select ‘Edinburgh’ and ‘Postgraduate Research’. ‘Programme’ presents you with a drop-down menu. Choose Bio-engineering and Bio-sciences PhD for study option(b) in ‘Research Project Information’You will be provided with a free text box for details of your research project. Enter Title of the project for which you are applying and also enter the supervisor’s name (Clare McCabe).This information will greatly assist us in tracking your application.For questions about the application process, please contact [email protected]