Computational Tools for the Biomedical Application of Carbon Nanomaterials

Abstract

Single-walled carbon nanotubes (SWNTs), with their versatile physico-chemical features, have been investigated as an efficient platform for biomedical applications. The main challenges of drug design are to locate compounds that bind selectively to target receptors, but not to other receptors such that they cause adverse side effects. If dispersed properly, nanoparticles of a certain size can pass through the blood barrier to deliver drugs to a targeted site. Often, drugs are rapidly released at lower pH, as in inflammatory/diseased and tumor cells. Nanoparticles are often functionalized and unfunctionalized with nonionic surfactant polymers, with and without functionalized hydrophobic drugs bound by cleavable linker, to render them stable in suspension. In biological membranes, cholesterol and amphiphilic molecules serve as surfactants and, by design, may be used to assist nanoparticles in carrying hydrophobic drugs to targeted sites. As the experimental investigation of biocompatible surfactants, and of hydrophobic drugs and their interactions with nanoparticles, is time-consuming and expensive, computer simulation might offer a viable means of understanding the interaction between nanoparticles (e.g., carbon nanotubes, fullerenes), drugs and biocompatible surfactants, either by covalent or noncovalent functionalization. Thus, an attempt was made to understand the various interaction properties of these complexes using computer simulation, perhaps to provide insight into the overall mechanisms and for experimental studies. The present study involved molecular dynamics (MD) simulations of a system composed of branched and unbranched PEGylated lipids, with and without the covalent and noncovalent functionalization of drugs [e.g., paclitaxel (PTX) and Irinotecan (Irin)] such as cholesterols and phospholipids (the components of the living cell's membrane) to single-walled carbon nanotubes (SWNTs). The behavior of these complexes in the presence of ssDNA and hormonally active vitamin D2 was also investigated. The addition of SWNTs and vitamin D2 leads to increases in the loading of PTX interaction and binding. Thus, a strategy was investigated to apply a comparative binding energy analysis of SWNTs to identify the interaction between different chemical species. The binding energy, mean square displacement, radial distribution function, angular and translational velocity autocorrelation functions of PEGylated cholesterol and phospholipid molecules are presented, and analyzed to understand the efficiency of the drug-delivery system in the presence of SWNTs, along with an historical perspective of its merits and demerits in biomedical applications. The strong interaction between complexed PTX in the presence of vitamin D2 and SWNTs is believed to be a determinant factor in the higher loading and prolonged burst release of the drug to a targeted site. Keywords: molecular modeling; carbon nanotubes; drug dispersion; biosurfactant; paclitaxel; irinotecan; calcitriol; ssDNA