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Investigation of drug encapsulation behavior is important to design efficient drug delivery materials. With this aim, we strive to perform coarse-grained simulations to study the drug encapsulation behavior of a particular micelle-forming co-polymer composed of hydrophilic PEG and hydrophobic PLGA units. The study is performed at the mesoscopic scale to overcome the time scale problem associated with the micelle formation at the atomistic scale. The structure and drug loading properties are studied at different polymer concentrations and drug loading. The resulting micellar structures that are obtained via dissipative particle dynamics simulations are observed to encapsulate the drug with high efficiency values. Moreover, the DPD simulations performed in this work reveal physical insight on the interactions and molecular structure as well as the temporal evolution of the encapsulation process. Our work can be considered as an attempt to computationally characterize the drug encapsulation behavior and structure of a prospective drug delivery system.

In this work, we employ coarse-grained dissipative particle dynamics simulations with the hydrogen bonds added explicitly to study the drug encapsulation property, structure, and interactions of Pluronic L64/ibuprofen combinations. The coarse-grained simulations reveal that the computed total drug encapsulation efficiency is around 80% and the simulations show a decrease in the micelle size upon encapsulation of the drug in line with the experimental literature. The computed radial distribution functions point out that the micelle shrinkage can be caused by an increased local packing of the hydrophobic-hydrophilic units around each other, and the absence of water molecules inside the micelles when there are drug molecules present in the system. Overall, the coarse-grained DPD simulations predict the structural and drug encapsulation properties of a polymeric system consistent with the experiments, whereby bringing new insights to its molecular understanding in terms of micelle shrinkage upon inclusion of ibuprofen.

In this paper, we present our efforts in modeling and simulation of polyethylene glycol crosslinked with an isocyanate tHDI. The polymer, by its nature, is hydrophilic and has strong hydrogen bond interactions with water. The simulations are performed at coarse-grained scale by using a dissipative particle dynamics (DPD) simulation method. The effect of hydrogen bond between water and polymer beads on the structure of the crosslinked hydrophilic polymer structure is studied. The polymer is observed to phase separate with water in the absence of hydrogen bonds in DPD simulations. In the reverse case, where hydrogen bonds are explicitly included in DPD simulations, polymer mixes with water. This behavior is investigated by plotting the density profiles. Moreover, the volumetric swelling behavior in mixtures with different water contents is estimated from simulations and extrapolated by a polynomial fit to compare with experiments. It is observed that the predicted swelling ratio is in good agreement with the experimental measurements.

Targeted drug delivery has become one of the key fields of personalized medicine. Developing candidate drug delivery agents requires a thorough understanding of the drug carrier materials by means of structure, drug encapsulation and release properties. To this aim, coarse-grained DPD simulations are employed to study the morphology, drug encapsulation and release of a particular amphiphilic block copolymer system. Extent of the drug encapsulation and release are observed to be mainly affected from copolymer concentration in the mixture. Mean aggregation number and average micelle volume are observed to increase as drug is encapsulated in the micelles. In addition, the shape of micelles is characterized as mainly spherical. It is observed that the drug release follows a pseudo-Fickian diffusion model and can be represented by the Korsmeyer-Peppas model. Furthermore, the diffusion rate of the drug molecules is observed to increase mainly in the release-phase. Our simulations can be viewed as a computational attempt to model the drug encapsulation and release by mimicking real experimental conditions, while yielding results on the structure and dynamics of the polymeric carrier. The results can be anticipated to find applications in understanding and controlling the parameters to design candidate drug delivery micelles at the molecular level.

We report the results of dissipative particle dynamics (DPD) parameterization and simulations of a mixture of hydrophilic polymer, PEG 400, and water which are known to exhibit negative volume excess property upon mixing. The addition of a Morse potential to the conventional DPD potential mimics the hydrogen bond attraction, where the parameterization takes the internal chemistry of the beads into account. The results indicate that the mixing of PEG and water are maintained by the influence of hydrogen bonds, and the mesoscopic structure is characterized by the trade-off of enthalpic and entropic effects. (C) 2017 Elsevier B.V. All rights reserved.

In this work, we report a parameterization procedure to compute the parameters of a hydrogel consisting of a hydrophilic polymer and a cross-linker. The system is parameterized so that coarse-grained dissipative particle dynamics (DPD) simulations can be performed. Proper computation of the simulation parameters is crucial in order to represent the inherent chemical nature of the hydrogel and to model the correct structure. The polymer is parameterized by considering different volumes for coarse-grained beads. Moreover, the hydrogen bond interactions should be represented and properly defined in the simulations. To that purpose, we use a recently introduced parameterization procedure that incorporates the attraction as a result of the hydrogen bond interactions between relevant beads. This paper serves as an example of how the realistic simulation parameters of a hydrophilic polymer can be straightforwardly computed by leading to a proper determination of the structure and properties. The computational background, the procedures and the results of the computation are reported and discussed in this paper.

Simulating water has always been a challenge. Due to the intrinsic hydrogen bond interactions, water exhibits structural properties, such as a tetrahedral coordination resulting in a specific Radial Distribution Function (RDF), which are not trivial to predict computationally. In this paper, we attempt to use coarse-grained Dissipative Particle Dynamics (DPD) simulations to parameterize the hydrogen bond interactions without violating the classical DPD framework. We model the hydrogen bond interactions by incorporating a Morse potential, where the parameters are computed by taking the experimental enthalpy of evaporation and hydrogen bond distances as reference. We show that with the proposed procedure the RDF, the coordination number, the isothermal compressibility, and the three-body angular distributions (to demonstrate the tetrahedral structure) of pure water are predicted in great extent compatible with the experiments. To test the applicability of the procedure to mixtures, we simulated pure methanol and methanol/water mixtures at different molar fractions. The predicted RDF profiles for methanol-methanol, methanol-water and water-water represent the characteristic experimental RDF behavior. Moreover, the calculated negative excess volumes as a function of mole fraction compare quite well with the experimentally observed excess volumes. Our findings motivate the further development and use of DPD simulations in modeling hydrogen bond interactions, which are crucial not only in water (or alcohols), but in more complex systems such as biomolecules, proteins or biopolymers. (C) 2020 Elsevier B.V. All rights reserved.

Thermodynamic stability of poloxamer micelles excluding and encapsulating ibuprofen drug at different concentrations is studied by means of free energies. Free energies are computed by a partitioning of the total free energy in order to consider the different parts of the co-polymers together with free co-polymer chains in solvent. Moreover, extra terms to the free energy are added to account for the drug-micelle and drug-solvent interactions. The thermodynamic stability of the system is found to be positively correlated with the drug loading for the same system. The RDFs computed between water and the drug molecules signify the decreasing neighboring between these pairs as the co-polymer and drug concentrations are increased in the mixtures as the system leans towards a higher thermodynamic stability. In this work, not only the thermodynamic stability but also its relation to the structure are discussed for a drug-laden system demonstrating the utility of the proposed procedure.

Simulation results for polyethylene glycol by employing a multi-scale approach combining mesoscopic and atomistic scales to characterize its structural, material and thermal properties in dry and wet environments are reported. After a meso-structure is created, DPD simulations with explicit hydrogen bond attraction are run for a molecular understanding of PEG oligomers. The meso-structure is analysed by the end-to-end distance and radius of gyration values, where we notice that water has an effect that makes the chains more flexible compared to the dry material, i.e., acts as a 'plasticizer' (as observed experimentally). Moreover, the helical formation of PEG chains is monitored by mesa-scale simulations and a larger distribution of helical chain formation is found for wet PEG. Following the DPD simulations, a reverse-mapping algorithm is used to insert atomistic detail into the mesoscopic configuration in order to run atomistic molecular dynamics simulations to calculate material properties. The comparison of the elastic properties in dry and wet environments shows that PEG becomes less compressible and more elastic upon addition of water. Moreover, the estimated coefficient of thermal expansion is in good agreement with the experimental value of a lower molecular weight PEG.

In this work we propose a computational approach to mimic hydrogen bonding in a widely used coarse-grained simulation method known as dissipative particle dynamics (DPD). The conventional DPD potential is modified by adding a Morse potential term to represent hydrogen bonding attraction. Morse potential parameters are calculated by a mapping of energetic and structural properties to those of atomistic scale simulations. By the addition of hydrogen bonding to DPD and with the proposed parameterization, the volumetric mixing behavior of low molecular weight alcohols and water is studied and experimentally observed negative volume excess is successfully predicted, contrary to the conventional DPD implementation. Moreover, the density-dependent DPD parameterization employed provides the asymmetrical shapes of the excess volume curves. In addition, alcohol surface enrichment at the air interface and self-assembly in the bulk is studied. The surface concentrations of alcohols at the air interface compare favorably with the experimental observations at all bulk-phase alcohol fractions and, in consonance with experiment, some clustering is observed.

In this paper we aim at predicting material properties of a cross-linked polymer by using multi-scale simulations and to compare the elastic properties and glass transition temperature with experimentally observed values. To that purpose we use an epoxy polymer for which the starting point is a mesoscopic simulation of its cross-linked structure realized by Dissipative Particle Dynamics (DPD) simulations, as recently improved to conserve local densities properly. This results in a coarse-grained structure of this thermoset polymer, relaxed at a large length- and long time-scale. Such a mesoscopic simulation is important as otherwise insufficient relaxation of the structures occurs for a later and proper comparison with experimental properties. Allowing further simulations at the atomistic scale using molecular dynamics (or any other method) to obtain material properties, a reverse-mapping procedure is required to insert atomistic detail into the coarse-grained structures. Hence, an efficient and reliable reverse-mapping procedure was implemented to be able to connect these two types of simulation. For the epoxy polymer chosen, Poisson’s ratio, the elastic modulus, the glass transition temperature and the thermal expansion coefficients of the glassy and rubbery state resulting from the equilibrated reverse-mapped structure, match the experimental values well. Overall, the paper reports a fast and straightforward procedure to bridge a mesoscopic structure to experimentally observed material properties, which can be applied to any system of interest.

We performed dissipative particle dynamics (DPD) simulations to investigate the structure and cross-link formation dynamics of a thermoset polymer while interacting with a metal-oxide surface. For characterizing the polymer–surface interactions we used the surface excess, quantifying the surface selectivity of different functional groups. Mesoscopic polymer–surface interactions are determined by matching the surface excess, as computed with atomistic molecular dynamics (MD), with those for DPD, thus realizing a coupling between the mesoscopic and atomistic scales. In the structure prior to cross-linking, we observe that some functional groups prefer to be located at the interface while others are repelled. This largely determines the final cross-linked structure near the metal-oxide interface. The initial preference for cross-links to form is in the bulk region. However, at longer times toward the equilibrium structure, the trade-off between the epoxy–alumina interactions causes migration of reacted groups to the surface.

Meso-scale simulations are performed to obtain a fully cross-linked, equilibrated structure of an epoxy network. We derive and study the interactions giving rise to the final structure. Both equilibrium structures with no cross-links and fully cross-linked are examined. The simulations were performed using a recent dissipative particle dynamics parameterization method in which beads attain their pure volumes in the final structure. Preferential attractive and repulsive behavior of different chemical functional groups is revealed. When those are simulated as monomers, two phases form where intra-bead interactions are attractive and inter-bead interactions are repulsive. A homogeneous density distribution over the simulation box is noticed when simulated as chains. The network properties are characterized as well. The cross-link conversions are analyzed which show that the bead type consisting of initially primary amines have the highest value. Moreover, different cross-link formation rates for secondary amines are incorporated in the simulations and effects on the structure and conversion are discussed.

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We use dissipative particle dynamics simulations to explore the phase behavior and solution properties of ABCBA type model surfactants in near-supercritical CO2 environment. We present design guidelines for functional surfactants with tunable properties. The block co-oligomers used in this study are made up of a CO2-phobic block having ethyl propionate and nine different types of ethylene monomers, flanked on either side by eight repeat units of fluorinated CO2-philic blocks. The most promising design block co-oligomer in the series is that with the longest CO2-phobic group in the ethylene monomers. For this particular oligomer, we systematically analyze the effect of concentration on the self-assembly behavior. Spherical micelles form in the 5%-65% volume fraction range for this oligomer, with the highest number of spherical micelles occurring at 45% surfactant in CO2. When the volume fraction of the surfactant is increased from 70% to 85%, cylindrical micelles occur. We further investigate the effect of the length of the solvophilic fluorinated segments on self-assembly and find that stable micelles occur in a window of 8-14 repeat units. We find that the most critical contribution to stability is due to the mixing free energy between the chain tails residing in the outer layers and the interpenetrating molecules. (C) 2009 American Institute of Physics. [doi:10.1063/1.3236518]