title: Transdermal cellular membrane penetration of proteins with gold nanoparticles: a molecular dynamics study.
abstract: Transdermal delivery, where the skin acts as the route for local or systemic distribution, presents a lot of advantages over conventional routes such as oral and intravenous and intramuscular injections. However, the delivery of large biomolecules like proteins through the skin is challenging due to their size and structural properties. A molecular level understanding of their transport across the skin barrier is desirable to design successful formulations. We have employed constrained and unconstrained coarse grained molecular dynamics simulation techniques to obtain the molecular mechanism of penetration of the horseradish peroxidase (HRP) protein into the skin, in the presence and absence of gold nanoparticles (AuNPs). Unconstrained simulations show that HRP, when considered individually, was not able to breach the skin barrier, while in the presence of AuNPs, it first binds to the AuNPs and then breaches the barrier. The constrained simulations revealed that there was a free energy barrier for HRP to permeate inside the skin lipid layer when taken alone, while in the presence of gold nanoparticles, no barrier was found. Our study opens up the field of computational modeling based design of nanoparticle carriers for a given protein's transdermal delivery.
authors.affiliation: Physical Science Research Area, TCS Research, Tata Research Development and Design Centre, 54B, Hadapsar, Pune, India. beena.rai@tcs.com.
authors.forename: Rakesh
authors.identifier: http://orcid.org/0000-0002-8637-7778
authors.initials: R
authors.lastname: Gupta
authors.affiliation: Department of Chemical Engineering, Indian Institute of Technology Delhi, New Delhi, India.
authors.forename: Nishi
authors.initials: N
authors.lastname: Kashyap
authors.affiliation: Physical Science Research Area, TCS Research, Tata Research Development and Design Centre, 54B, Hadapsar, Pune, India. beena.rai@tcs.com.
authors.forename: Beena
authors.initials: B
authors.lastname: Rai
mesh_terms: D000818:Animals; D006046:Gold / Q000737:chemistry*; D006735:Horseradish Peroxidase / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D012867:Skin / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers; D006046:Gold; D006735:Horseradish Peroxidase