Computational and experimental approaches for investigating nanoparticle-based drug delivery systems

Abstract

Most therapeutic agents suffer from poor solubility, rapid clearance from the blood stream, a lack of targeting, and often poor translocation ability across cell membranes. Drug/gene delivery systems (DDSs) are capable of overcoming some of these barriers to enhance delivery of drugs to their right place of action, e.g. inside cancer cells. In this review, we focus on nanoparticles as DDSs. Complementary experimental and computational studies have enhanced our understanding of the mechanism of action of nanocarriers and their underlying interactions with drugs, biomembranes and other biological molecules. We review key biophysical aspects of DDSs and discuss how computer modeling can assist in rational design of DDSs with improved and optimized properties. We summarize commonly used experimental techniques for the study of DDSs. Then we review computational studies for several major categories of nanocarriers, including dendrimers and dendrons, polymer-, peptide-, nucleic acid-, lipid-, and carbon-based DDSs, and gold nanoparticles. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov.

Molecular Mechanism of Polycation-Induced Pore Formation in Biomembranes

“…The polymer−membrane interaction at the molecular scale can be investigated by performing atomistic molecular dynamics (MD) simulations. 17 However, modeling the complete sequence of events in polycation−bilayer systems, namely, adsorption from solution on the bilayer, followed by insertion into the bilayer interior and eventual pore formation, is currently beyond the time scales accessible through equilibrium atomistic MD simulations. 18 Although the initial steps, i.e., polymer adsorption and insertion, have been simulated with equilibrium MD, 14,16 special enhanced sampling techniques such as the umbrella sampling method are required to model pore formation in the presence of polycations.…”

Conjugation of pectin biopolymer with Au‐nanoparticles as a drug delivery system: Experimental and DFT studies

“…Computer simulations present important details such as drug‐loading capacity, distribution/complex structure and release mechanism and the rate of the drug release from nanoparticles in drug‐delivery systems . In the present study, the adsorption behaviors of the pectin biopolymer on the surface of the gold nanoparticles were investigated using DFT calculation.…”

Raman spectroscopy and density functional theory study of energetically closely separated C2′‐endo and C3′‐endo pentose forms in purine nucleoside analogue drug‐gold conjugates

“…Over the past several decades, the chemical synthesis has led to the discovery and development of cancer therapeutic agents based on the understanding of drug uptake, molecular interaction, and cellular process . Much attention has been paid to the application of nanoparticulate intracellular delivery of anticancer drugs to cure cancers …”