Molecular mechanism of transdermal co-delivery of interferon-alpha protein with gold nanoparticle – a molecular dynamics study

Abstract

The transdermal route provides numerous advantages over conventional drug delivery routes. However, passive delivery of large molecules such as proteins through the skin is challenging due to its barrier function. Therefore, to design a successful formulation, molecular interaction of these proteins with constituent molecules present in the skin responsible for its barrier function, is necessary. In this study, we have shown through extensive computer simulations that the therapeutic protein, interferon alpha (INF), can be co-delivered through the skin using the gold nanoparticle. We carried out both steered (umbrella sampling) and unrestrained coarse-grained molecular dynamics simulation to show the molecular mechanism of absorption/permeation of protein on/through skin layer in the absence/presence of gold nanoparticle. According to the steered simulations, when INF was taken alone, the free energy minimum was observed at the head group of the skin layer, whereas, when co-delivered with AuNP, it was observed in the interior of the bilayer. Unrestrained simulations have also shown that INF was adsorbed on the skin lipid bilayer head group, while in presence of AuNP, it first complexed with the AuNP and then breached the barrier. The MD simulations thus established the transdermal delivery as a possible pathway for delivery of INF protein.

Keywords:

• Molecular dynamics
• transdermal protein delivery
• gold nanoparticles

Acknowledgement

The current work was funded by TCS-CTO organisation. Authors would like to thank High Performance Computing Facility at Tata Consultancy Services (TCS) for providing access to EKA Super computer. They would also like to thank Mr. K Ananth Krishanan, CTO, TCS for his constant encouragement and support during this project.