Assessing the Efficacy of Poly(N-isopropylacrylamide) for Drug Delivery Applications Using Molecular Dynamics Simulations
| Autor: | Soroush Moghadam, Ronald G. Larson |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Materials science
Polymers Acrylic Resins Pharmaceutical Science 02 engineering and technology Molecular Dynamics Simulation 010402 general chemistry Mole fraction 01 natural sciences Lower critical solution temperature Excipients chemistry.chemical_compound Molecular dynamics Drug Delivery Systems Drug Discovery Polymer chemistry Thermoresponsive polymers in chromatography chemistry.chemical_classification Acrylamides Comonomer Temperature Water Polymer 021001 nanoscience & nanotechnology 0104 chemical sciences Solutions Drug Liberation chemistry Chemical engineering Drug delivery Poly(N-isopropylacrylamide) Molecular Medicine 0210 nano-technology Hydrophobic and Hydrophilic Interactions |
| Zdroj: | Molecular Pharmaceutics. 14:478-491 |
| ISSN: | 1543-8392 1543-8384 |
| Popis: | All-atom molecular dynamic simulations (AA-MD) are performed for aqueous solutions of hydrophobic drug molecules (phenytoin) with model polymer excipients, namely, (1) N-isopropylacrylamide, (pNIPAAm), (2) pNIPAAm-co-acrylamide (Am), and (3) pNIPAAm-co-dimethylacrylamide (DMA). After validating the force field parameters using the well-known lower critical solution behavior of pNIPAAm, we simulate the polymer-drug complex in water and its behavior at temperatures below (295 K) and above the LCST (310 K). Using radial distribution functions, we find that there is an optimum comonomer molar fraction of around 20-30% DMA at which interaction with phenytoin drug molecules is strongest, consistent with recent experimental findings. The results provide evidence that molecular simulations are able to provide guidance in the optimization of novel polymer excipients for drug release. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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