Molecular Modeling in Drug Delivery: Polymer Protective Coatings as Case Study

The goal of this chapter is to demonstrate the potential of large-scale molecular dynamics (MD) simulation as a design tool in pharmaceutics using the specific example of the use of polymers in drug delivery applications. We first present an overview of the challenge of drug delivery and the roles polymers play in easing the constraints of what we describe as the balancing act of drug delivery. We then present an overview of the different polymers used in drug delivery applications and the roles they play; we describe the variety of drug delivery systems that make use of polymeric coatings. We then discuss MD simulation as a tool within the context of mechanistic understanding, a paradigm for the development of drug delivery strategies. We provide an overview of how MD simulation is performed and how parameter sets of molecules are constructed, with specific details relevant to the construction of models of polymers highlighted. For the remainder of the chapter, we highlight examples of the use of MD simulation of polymers used as protective sheaths for a wide range of drug delivery mechanisms. This includes liposomes, lipid nanoparticles, polymeric micelles, dendrimers, protein-based systems, and finally inorganic nanoparticles, including carbon architectures and silica and gold nanoparticles. We suggest past review papers written by us where we have covered the broader issue of the use of MD simulation for drug delivery as further reading on this topic.