Molecular dynamics simulation of drug uptake by polymer

Abstract

Drug uptake by polymer was modeled using a molecular dynamics (MD) simulation technique. Three drugs--doxorubicin (water soluble), silymarin (sparingly water soluble) and gliclazide (water insoluble)--and six polymers with varied functional groups--alginic acid, sodium alginate, chitosan, Gantrez AN119 (methyl-vinyl-ether-co-malic acid based), Eudragit L100 and Eudragit RSPO (both acrylic acid based)--were selected for the study. The structures were modeled and minimized using molecular mechanics force field (MM+). MD simulation (Gromacs-forcefield, 300 ps, 300 K) of the drug in the vicinity of the polymer molecule in the presence of water molecules was performed, and the interaction energy (IE) between them was calculated. This energy was evaluated with respect to electric-dipole, van der Waals and hydrogen bond forces. A good linear correlation was observed between IE and our own previous data on drug uptake(*) [R² = 0.65, R²adj = 0:65; R²pre = 0:56 and a F ratio of 30.25, P < 0.001; Devarajan et al. (2005) J Biomed Nanotechnol 1:1-9]. Maximum drug uptake by the polymeric nanoparticles (NP) was achieved in water as the solvent environment. Hydrophilic interaction between NP and water was inversely correlated with drug uptake. The MD simulation method provides a reasonable approximation of drug uptake that will be useful in developing polymer-based drug delivery systems.

Selective Interactions of Zein Microspheres with Different Class of Drugs: An In Vitro and In Silico Analysis

“…Subhashini et al (11) applied molecular dynamics simulation to study the drug uptake by different polymers such as alginate, eudragit, etc. Samina et al (12) studied the encapsulation of prednisolone, paracetamol, and isoniazid in poly (L-lactic acid) microspheres using molecular dynamics technique.…”

Molecular dynamics simulation study of chitosan and gemcitabine as a drug delivery system

“…In addition, MD simulations can be applied to investigate the behavior of complex materials in molecular scale in various branches of sciences especially nanotechnology and biology [24]. Attempts have been made to study drug delivery systems by using MD simulations: Subashini et al [27] investigated the interaction between drugs (doxorubicin, silymarin, and gliclazide) and six polymers (chitosan, alginic acid, sodium alginate, Gantrez AN119, Eudragit L100, and Eudragit RSPO) and they determined the best polymer for each drug by comparing the results obtained for the interaction energy and the percentage encapsulation efficiency. Macháčková et al [29] studied six biodegradable polymers (chitosan, L-polylactide, D-polylactide, polyglycolic acid, polyethylene glycol, and cellulose) as carriers for cyclosporine A and they found a relationship between mixing energy, chain length, and chain flexibility of the studied polymer/drug delivery systems.…”

“…Stability is closely related to the physicochemical properties of the microenvironment in the delivery system, and to the interactions between the drug and the polymer [27].…”

“…Molecular dynamics (MD) simulation can be used to study the structure and key properties of materials such as their stability, diffusion, and interactions between their molecules. MD simulation, without paying a high price for experimental methods, can be used to optimize drug delivery systems and subsequently to study the properties of the drug and its interaction with other molecules [27]. In addition, MD simulations can be applied to investigate the behavior of complex materials in molecular scale in various branches of sciences especially nanotechnology and biology [24].…”

Investigating the release of a hydrophobic peptide from matrices of biodegradable polymers: An integrated method approach

“…Molecular dynamics (MD) simulations demonstrated their power to represent real systems and to provide useful insights into molecular structures [35]. MD simulations of polymers have a relatively long and well established history from monitoring protein folding [36, 37] to investigations of mechanical properties of amorphous polymer solids [34, 38], to elucidation of structure and conformations in polymer solutions [39], and to studies of specific interactions in polymer blends and molecular complexes [40–43]. Distinctive features and the character of hydrogen-bonding networks in polymer-containing molecular systems have been the focus of several studies [35, 44–47].…”