Diffusion of small molecules in bioartificial membranes for clinical use: molecular modelling and laboratory investigation

Ioniță, Mariana; Silvestri, Davide; Gautieri, Alfonso; Votta, Emiliano; Ciardelli, Gianluca; Redaelli, Alberto

doi:10.1016/j.desal.2006.03.280

Cited by 4 publications

(3 citation statements)

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“…The initial geometries of the bulk models are refined following a procedure which consists in a series of MD calculations at different temperature and ensembles in order to obtain chain redistribution within the periodic cell [13,17,20,21]. Specifically, we perform a preliminary minimization of the systems (using the steepest descent algorithm) followed by a sequence of nine MD simulations (see Table 1).…”

Section: Models Equilibrationmentioning

confidence: 99%

Atomistic modeling of water diffusion in hydrolytic biomaterials

et al. 2011

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One of the most promising applications of hydrolytically degrading biomaterials is their use as drug release carriers. These uses, however, require that the degradation and diffusion of drug are reliably predicted, which is complex to achieve through present experimental methods. Atomistic modeling can help in the knowledge-based design of degrading biomaterials with tuned drug delivery properties, giving insights on the small molecules diffusivity at intermediate states of the degradation process. We present here an atomistic-based approach to investigate the diffusion of water (through which hydrolytic degradation occurs) in degrading bulk models of poly(lactic acid) or PLA. We determine the water diffusion coefficient for different swelling states of the polymeric matrix (from almost dry to pure water) and for different degrees of degradation. We show that water diffusivity is highly influenced by the swelling degree, while little or not influenced by the degradation state. This approach, giving water diffusivity for different states of the matrix, can be combined with diffusion-reaction analytical methods in order to predict the degradation path on longer time scales. Furthermore, atomistic approach can be used to investigate diffusion of other relevant small molecules, eventually leading to the a priori knowledge of degradable biomaterials transport properties, helping the design of the drug delivery systems.

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Section: Models Equilibrationmentioning

confidence: 99%

Atomistic modeling of water diffusion in hydrolytic biomaterials

et al. 2011

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“…Atomistic simulation have been successfully applied in the past to obtain the diffusion coefficients of small molecules (like oxygen, carbon dioxide or water) in polymeric membranes [1][2][3][4][5][6][7], polymeric blends [8,9], biopolymers [10,11] and organic-inorganic hybrid membranes [12]. However, despite the increasing computational power available to researchers and the improvements in the MD codes, atomistic simulations are still able to handle only systems with tens or hundreds of thousands of atoms and in the nanoseconds time scale.…”

Section: Introductionmentioning

confidence: 99%

How to predict diffusion of medium-sized molecules in polymer matrices. From atomistic to coarse grain simulations

2010

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The normal diffusion regime of many small and medium-sized molecules occurs on a time scale that is too long to be studied by atomistic simulations. Coarse-grained (CG) molecular simulations allow to investigate length and time scales that are orders of magnitude larger compared to classical molecular dynamics simulations, hence providing valuable approach to span time and length scales where normal diffusion occurs. Here we develop a novel multi-scale method for the prediction of diffusivity in polymer matrices which combines classical and CG molecular simulations. We applied an atomistic-based method in order to parameterize the CG MARTINI force field, providing an extension for the study of diffusion behavior of penetrant molecules in polymer matrices. As case study, we found the parameters for benzene (as medium sized penetrant molecule whose diffusivity cannot be determined through atomistic models) and Poly (vinyl alcohol) (PVA) as polymer matrix. We validated our extended MARTINI force field determining the self diffusion coefficient of benzene (2.27E-9 m^2/s) and the diffusion coefficient of benzene in PVA (0.263E-12 m^2/s). The obtained diffusion coefficients are in remarkable agreement with experimental data (2.20E-9 m^2/s and 0.25E-12 m^2/s, respectively). We believe that this method can extend the application range of computational modeling, providing modeling tools to study the diffusion of larger molecules and complex polymeric materials. AbstractThe normal diffusion regime of many small and medium-sized molecules occurs on a time scale that is too long to be studied by atomistic simulations. Coarse-grained (CG) molecular simulations allow to investigate length and time scales that are orders of magnitude larger compared to classical molecular dynamics simulations, hence providing valuable approach to span time and length scales where normal diffusion occurs. Here we develop a novel multiscale method for the prediction of diffusivity in polymer matrices which combines classical and CG molecular simulations. We applied an atomistic-based method in order to parameterize the CG MARTINI force field, providing an extension for the study of diffusion behavior of penetrant molecules in polymer matrices. As case study, we found the parameters for benzene (as medium sized penetrant molecule whose diffusivity cannot be determined through atomistic models) and Poly (vinyl alcohol) (PVA) as polymer matrix. We validated our extended MARTINI force field determining the self diffusion coefficient of benzene m 2 s -1 and 0.25·10 -12 m 2 s -1 , respectively). We believe that this method can extend the application range of computational modeling, providing modeling tools to study the diffusion of larger molecules and complex polymeric materials.

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“…Model Equilibration: Fully atomistic simulations are carried out using NAMD. The initial geometries of the models are refined following a procedure previously implemented and tested which consists of MD calculations at different temperature and groups to obtain chain redistribution within the periodic cell (Entrialgo-Castano et al 2006;Entrialgo-Castaño et al 2008;Gautieri et al 2010;Gautieri et al 2011;Ionita et al 2017). The molecular models were minimized and equilibrated using the NAMD code under constant pressure and temperature (NPT) conditions in order to relax the volume of the periodic box (Nelson et al 1996).…”

Section: Model Generationmentioning

confidence: 99%

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Supplemental Information 2: Raw Data - Semipermeable Membrane

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The osmotic pressure of chondroitin sulfate glycosaminoglycans (CS-GAGs) in a simulated physiological environment of articular cartilage is thoroughly examined in silico using full atomistic models. The effects of chemical and physical properties were investigated to elucidate the molecular origins of cartilage biomechanical behavior providing singleatomistic resolution analyses which would not be attainable with in vivo or in in vitro techniques. CS-GAG chains exhibit plastic deformation behavior under compressive load in the extracellular matrix (ECM) and osmotic pressure is the main contributor in balancing external pressures. This study focuses on quantitatively expressing this contribution. Molecular dynamics was used to imitate the physiological environment experienced by GAGs inside articular cartilage by simulating a semipermeable membrane acting on the full atomistic chains during compression. To this end, a variety of validation techniques, pre-simulation tasks, and comparisons were conducted to validate the test methodology. CS-GAGs with varying lengths and sulfation positions underwent simulation under varying molar concentrations. Sulfation positioning is found to have negligible influence on GAG osmotic pressure behavior; attributed to the small distance between the position of 4-and 6-sulfation relative to the intermolecular spacing between the CS chains. However, differences between sulfated and unsulfated chains did have a significant influence on osmotic pressure. Length of disaccharides was also found to have a significant contribution to osmotic pressure. Measurements are comparable to previous coarse grained studies and experimental data.

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Diffusion of small molecules in bioartificial membranes for clinical use: molecular modelling and laboratory investigation

Cited by 4 publications

References 1 publication

Atomistic modeling of water diffusion in hydrolytic biomaterials

Atomistic modeling of water diffusion in hydrolytic biomaterials

How to predict diffusion of medium-sized molecules in polymer matrices. From atomistic to coarse grain simulations

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