Validation of a Novel Molecular Dynamics Simulation Approach for Lipophilic Drug Incorporation into Polymer Micelles

Abstract

Polymer micelles can be used to facilitate the aqueous solubilization of lipophilic, poorly water-soluble compounds and drugs. Even if the evaluation of the efficiency of drug incorporation into such micelles can be tested experimentally, a theoretical approach based on molecular simulation can constitute a useful tool that reduces time and cost. Here we present a promising method, based on molecular dynamics simulation, for the calculation of the Flory-Huggins interaction parameters as a measure of the potential for drug incorporation into polymer micelles. The data from modeling are validated on four drug compounds with different physical-chemical properties by means of a comparison with the data obtained from experiments.

Water Uptake, Distribution, and Mobility in Amorphous Poly( d , l ‐Lactide) by Molecular Dynamics Simulation

“…Recent years have witnessed a growing interest in the field of biodegradable polymers and, consequently, in computational activities to explore various molecular properties of biodegradable polymers . Poly(lactide) (PLA) and its copolymers are among the most widely used synthetic biodegradable polymers for drug encapsulation and delivery with several products for controlled release of proteins or peptides on the market .…”

Computational Amphiphilic Materials for Drug Delivery

“…However, vitamin D3 exhibited the highest loading even with less strong H-bonding and π-π interactions. Thus, the study revealed the significant role of subtle structural characteristics (e.g., size, flexibility, and rigidity) in drug loading and suggested the computations of drug-polymer pairs would be a powerful prescreening tool in the development and optimization FiGURe 3 | Snapshot of cyclosporin A (in van der waals surface) and PeG-hexPLA (PeG in blue and hexPLA in red) mixture (Kasimova et al, 2012). Reproduced with permission from American Chemical Society.…”

“…A linear relationship was observed between the solubility and mass fraction for the four drugs. This method could be further utilized to estimate drug incorporation efficiency upon structural modification of polymer chains (Kasimova et al, 2012). The above computational studies reported drug solubility, miscibility, and compatibility in different copolymers.…”

Molecular dynamics simulation of some cyclic compounds solubilization into the nanometric core of Cetyltrimethylammonium Bromide micelle

“…1 molecule) there is no significant change in micellar size. Consequently, we will just investigate the size and shape of micelle for systems [6][7][8][9].…”

“…There are many theoretical and experimental studies on the solubilization and solubilization location of hydrophobic materials such as drugs [7,8], dyes [9,10], oils [11] and other organic compounds [12][13][14][15][16] within the micelles. Recognizing of these solubilization sites is very essential and helps us to have a better understanding of solubilizate characteristics in micelle, to investigate reaction mechanism in micellar systems and to design the micellar systems to reach the favorite properties.…”