Mesoscale Simulation and cryo-TEM of Nanoscale Drug Delivery Systems

Abstract

This work sets out to study the effect of hydrophobic molecules on the morphology of aqueous solutions of amphiphilic block copolymer, which has potential drug delivery applications. The effect is studied both experimentally and by using simulations. Using cryogenic TEM observations, micelles can clearly be visualised and their core size measured. While pure polymer solutions form into spherical micelles with a narrow size distribution, addition of small amounts of hydrophobic drug molecules leads to distortions in shape, a wider size distribution, and larger average core diameter. Simulations are based on a mesoscale dynamic density functional method with Gaussian chain Hamiltonian and mean-field interactions, as implemented in the MesoDyn code. With parameters for the amphiphilic system established in earlier work, and mean-field interactions for the drug molecule derived from structure -property relationships, we obtain good agreement with the TEM observations for the effect of the hydrophobic molecules on the morphology. The simulations clearly show how increasing drug concentration leads to an increase in micelle size, a wider distribution and more elongated rather than spherical micelles.

Predicting the Solubility of the Anti-Cancer Agent Docetaxel in Small Molecule Excipients using Computational Methods

“…In a few cases, computer simulations have been employed to predict other properties of drug delivery systems (e.g. morphology, stability and interactions) at the molecular and coarse-grain levels (19)(20)(21)(22). For example, Poupaert and Couvreur calculated the interaction energy between the anticancer drug doxorubicin and n-butyl polycyanoacrylate using molecular simulations (15).…”

Experimental study and dissipative particle dynamics simulation of the formation and stabilization of gold nanoparticles in PEO–PPO–PEO block copolymer micelles

“…On the basis of those values, both DPD (Cao et al, 2005) and Mesodyn (Lam et al, 2004) simulations allowed describing the aggregation process of PEO-PPO-PEO block copolymers in aqueous solution. Thus those values were retained in our work.…”

“…The parameters for EO-water, PO-water and EO-PO were estimated from the correlations of polymer solubility parameters (Lam et al, 2004) or a simulation method coded as Blend module in Cerius 2 (Cao et al, 2005). On the basis of those values, both DPD (Cao et al, 2005) and Mesodyn (Lam et al, 2004) simulations allowed describing the aggregation process of PEO-PPO-PEO block copolymers in aqueous solution.…”

Solubilization of saikosaponin a by ginsenoside Ro biosurfactant in aqueous solution: Mesoscopic simulation

“…Mesoscopic simulations have been used to study the aggregation behavior of polymeric surfactants before [14][15][16][17][18][19][20][21][22][23][24]. As computing power has increased, mesoscopic simulation has formed a bridge between speedy molecular kinetics and slow thermodynamic relaxation of macroscale properties.…”