Chitosan/glycyrrhizic acid hydrogel: Preparation, characterization, and its potential for controlled release of gallic acid.

In the present work, chitosan (CHT) as a biodegradable polymer was crosslinked using various amounts of glycyrrhizic acid (GLA) as a novel crosslinking agent to prepare biocompatible hydrogels. The prepared hydrogels were used for the controlled release of gallic acid (GA) in transdermal therapy application. FTIR, XRD, and SEM were used to characterize the prepared gels. The results indicated that the carboxylic acid groups of GLA react with the amine groups of the CHT in the presence of activating coupling reagents to form covalent amide linkage between the polymer chains of CHT and construct CHT cross-linked hydrogel (CCH) network structure. The prepared CCH samples were characterized and used for the controlled release of a drug, i.e. (GA). For this purpose, the swelling kinetic, loading and encapsulation efficiency, in vitro drug release, drug release kinetics, cell viability assay, and anti-bacterial activity of the samples were evaluated. The swelling ratio of CCH samples were in the range of 455-37 % depending on the pH of environment. Swelling kinetic results showed an aggregate to the non-linear second-order kinetic model. Drug release results were fitted by kinetic models while the Korsmeyer-Peppas model was fitted better. The CCH samples exhibited high biocompatibility for 5 mg/ml hydrogel concentration. In addition, the CHT and CCH sample without the GA did not show anti-bacterial properties for 1200 and 150 µg/ml concentrations, respectively. The CCH sample containing the GA exhibited enough anti-bacterial activity on the S. aureus bacteria strain at 150 µg/ml concentration. In contrast, the CCH sample containing the GA has a light anti-bacterial effect on the E. coli bacteria strain. The calculated mesh size of hydrogel networks, drug size, and kinetics models revealed that the CCH samples could release GA based on a diffusion mechanism. In conclusion, the designed CCH samples have enough ability for controlled drug release in transdermal applications.

Customizing nano-chitosan for sustainable drug delivery.

Chitosan is a natural polymer with acceptable biocompatibility, biodegradability, and mechanical stability; hence, it has been widely appraised for drug and gene delivery applications. However, there has been no comprehensive assessment to tailor-make chitosan cross-linkers of various types and functionalities as well as complex chitosan-based semi- and full-interpenetrating networks for drug delivery systems (DDSs). Herein, various fabrication methods developed for chitosan hydrogels are deliberated, including chitosan crosslinking with and without diverse cross-linkers. Tripolyphosphate, genipin and multi-functional aldehydes, carboxylic acids, and epoxides are common cross-linkers used in developing biomedical chitosan for DDSs. Methods deployed for modifying the properties and performance of chitosan hydrogels, via their composite production (semi- and full-interpenetrating networks), are also cogitated here. In addition, recent advances in the fabrication of advanced chitosan hydrogels for drug delivery applications such as oral drug delivery, transdermal drug delivery, and cancer therapy are discussed. Lastly, thoughts on what is needed for the chitosan field to continue to grow is also debated in this comprehensive review article.

Role of physicochemical characteristics of poly(N,N-diethylacrylamide) on the polymer thermal responsivity and interfacial properties in aqueous solution: All-atom simulation study.

Molecular dynamic behaviors of poly(N,N-diethylacrylamide) (PDEA) as well as its interfacial properties in water were studied measuring the polymer single chain in a dilute concentration regime via molecular dynamics simulation. The investigation of chain length and temperature impacts on the rate of affinity variation of PDEA to water through calculating non-bonded interactions between them showed that the increment of two mentioned items reduced the polymer hydrophilicity in water. The interactional variation altered the PDEA diffusivity in the solution so that the decrement of PDEA tendency to water enhanced the chain movements because of reducing the interfacial friction between the chain and media, particularly at the transition zone. The chains spatial dimensions, conformation and shape were determined as a function of temperature to evaluate the chain hydrodynamic features. A particular order parameter for the PDEA backbone bonds and distribution of their dihedral angles were calculated to consider entropy of the chains with temperatures. The results indicated that PDEA tended to have a rod conformation with less entropy at lower temperatures and chain lengths. Finally, a novel parameter, < Pθφ(T) >, based on the interfacial structure of water was presented to quantitate the relationship between the thermodynamics of PDEA and its structure and hydrophilicity variation with temperature.

A simulation study on hydrogel performance for enhanced oil recovery using phase-field method.

Hydrogels are increasingly applied in oil recovery processes. This leads to more controlled flow of fluids in porous media. In this process, hydrogel is injected to the reservoir to block the high permeability areas. The trapped oil in low permeability regions, is then swept by water flooding. pH-sensitive hydrogel microspheres were synthesized in another work of the authors, which effectively increased the oil recovery factor in experimental studies. In this communication, phase-field approach was used to simulate this process and to obtain the tuning parameters of the model including thickness of the contact surface (є), phase transform parameter (M0), and excess free energy (∧). Diffusion of hydrogels was studied by Cahn-Hilliard conservative approach and the breakage, deformation, and plugging mechanisms were analyzed, based on pressure drop variations in micromodel. Moreover, Effective parameters on oil recovery factor were analyzed. Results indicated a good agreement between experimental and modeling studies of oil recovery factor in water and hydrogel flooding with absolute errors of 2.29% and 4.06%, respectively. The recovery factor was calculated using a statistical method which was in good agreement with the modeling results. The tuned parameters of the model were reported as, є = 111.7 µm, M0 = 5 × 10-13 m3/s, [Formula: see text] J/m3.

A coarse-grain force field based on quantum mechanics (CGq FF) for molecular dynamics simulation of poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) micelles.

In order to provide the means to predict from molecular dynamics (MD) simulations the structures of copolymer-based micelles in solution, we developed coarse grain force field (CGq FF) parameters for poly(ethylene glycol) (PEG) and for poly(ε-caprolactone) (PCL). A key advance here is the use of quantum mechanics to train the parameters describing the non-bonded (NB) interactions between the CG beads. The functional forms are the same as the MARTINI CG FF so standard MD codes can be used. Our CGq FF describes well the experimentally observed properties for the polymer-air and polymer-water interfaces, indicating the accuracy of the NB interactions. The structural properties (density, radius of gyration (Rg), and end-to-end distance (h)) match both experiment and all atom (AA) simulations. We illustrate the application of this CGq FF by following the formation of a spherical micelle from 250 chains of PEG23-b-PCL9 diblock copolymer, each block with molecular weight of 1000 Daltons (10 500 beads, corresponding to 123 250 atoms), in a water box with 119 139 water beads (426 553 water molecules).

Dissolution and conformational behavior of functionalized cellulose chains in the bulk, aqueous and non-aqueous media: A simulation study.

In the present study, we employ all-atom molecular dynamics simulations to investigate the dynamic behaviors and structural properties of the native and modified cellulose chains in the bulk, aqueous, and organic media. Particular attention has been directed to the role of different hydrophobic and hydrophilic functional groups as linear and branched aliphatic and also cyclic pendent groups on the solubility and packing of the cellulose chain. The various properties related to density profile, mean squared displacement, intramolecular entropy, radius of gyration, and radial distribution function were calculated. The results showed that the chain tendency toward crystallinity decreased when the native cellulose chains were modified using functional groups. This issue is supported by the fact that modifying the chains decreases the compactness of the cellulose chains due to partial solubility increasing of the modified chains, especially for the chains functionalized by polyether groups. The present computational data highlights the crucial role of the functional groups with the hydrophilic nature and linear molecular architecture to reduce the cellulose chains compactness in both aqueous and organic media when compared with the other types of functional groups.

Molecular dynamics simulation of polystyrene copolymer with octyl short-chain branches in toluene.

In this study, dimensional, conformational and dynamic behaviors of a short-chain branched styrene/1-octene copolymer chain with different 1-octene percentages, i.e., 0, 2, 4 and 6%, in toluene are investigated at the temperature of 298.15 K via molecular dynamics simulation. The chain dimensions and flexibility in the solvent are evaluated by calculating the radius of gyration (Rg), end-to-end distance (), surface area (Ach), and volume (Vch) of the copolymer chain. The mean square displacement (MSD) and diffusivity coefficient for each copolymer chain are measured to determine its dynamic behavior and mobility in aromatic media. To consider the effect of increasing the 1-octene co-monomer percentage on the copolymer chain affinity to the solvent molecules, the interaction energy (Eint) and Flory-Huggins (FH) interaction parameter are calculated for each equilibrated solution model. The simulation results indicate that the co-monomer level increment in the copolymer structure reduces the chain Rg amount and its interaction with the solvent. The of the chain increases up to 4% co-monomer content, while further co-monomer content decreases the value. Additionally, the viscosity of the equilibrated dilute solutions is calculated via non-equilibrium molecular dynamics simulation (NEMD). Moreover, the steric hindrance of the copolymers and the solvent molecules capturing in the dilute solution is determined via radial distribution function (RDF) analysis. Helmholtz free energy and the system entropy changes are calculated to evaluate the tendency of the copolymer to the solvent molecules and its dilute solution irregularity, respectively. Graphical abstract The figure shows the variations trend of the poly(styrene-co-1-octene) chain dimensions in toluene aromatic solvent by increasing the 1-octene content (x), after the equilibration state. Red and blue colors represent the carbon atoms of the copolymer chain backbone and 1-octene side chains, respectively. The styrene rings and the hydrogen atoms of the chains were removed for better view.

Dual responsive PMEEECL-PAE block copolymers: a computational self-assembly and doxorubicin uptake study.

The self-assembly behaviour of dual-responsive block copolymers and their ability to solubilize the anticancer drug doxorubicin (DOX) has been investigated using all-atom molecular dynamics (MD) simulations, MARTINI coarse-grained (CG) force field simulation and Scheutjens-Fleer self-consistent field (SCF) computations. These diblock copolymers, composed of poly{γ-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-ε-caprolactone} (PMEEECL) and poly(ß-amino ester) (PAE) are dual-responsive: the PMEEECL block is thermoresponsive (becomes insoluble above a certain temperature), while the PAE block is pH-responsive (becomes soluble below a certain pH). Three MEEECL20-AE M compositions with M = 5, 10, and 15, have been studied. All-atom MD simulations have been performed to calculate the coil-to-globule transition temperature (T cg) of these copolymers and finding appropriate CG mapping for both PMEEECL-PAE and DOX. The output of the MARTINI CG simulations is in agreement with SCF predictions. The results show that DOX is solubilized with high efficiency (75-80%) at different concentrations inside the PMEEECL-PAE micelles, although, interestingly, the loading efficiency is reduced by increasing the drug concentration. The non-bonded interaction energy and the RDF between DOX and water beads confirm this result. Finally, MD simulations and SCF computations reveal that the responsive behaviour of PMEEECL-PAE self-assembled structures take place at temperature and pH ranges appropriate for drug delivery.

A deep insight into the polystyrene chain in cyclohexane at theta temperature: molecular dynamics simulation and quantum chemical calculations.

Molecular characteristics of an atactic polystyrene (aPS) chain with different lengths in a theta solvent, cyclohexane at 307.65 K, were studied via molecular dynamics (MD) simulation. The interaction energy of the aPS dilute solution models and Flory-Huggins (FH) interaction parameter were calculated to investigate the effect of the chain molecular weight on its compatibility with the solvent molecules. The simulation results illustrated that increasing the chain length increased the interactions between the chain and the solvent molecules. The chain dimensions via calculating the radius of gyration (Rg) and end-to-end distance, , were measured. Mean square displacement (MSD) and diffusivity coefficient of the chains were calculated to determine their dynamic behavior. The results exhibited that two factors of the chain movability and size were important for the diffusion in oligomeric state. Additionally, viscosity of the resultant dilute solutions was calculated via nonequilibrium molecular dynamics simulation (NEMD). Moreover, the steric hindrance of the chains was determined by radial distribution function (RDF) analysis. The calculated characteristics of the chain and solution viscosity results showed a good agreement with experimental published works. Measurement of the potential field of cyclohexane-cyclohexane and aPS-cyclohexane pairs was also based on their potential field via quantum chemical calculations to determine the special orientation of the solvent molecules to each other and to the polymer segments, respectively. Graphical abstract (a) The equilibrated dilute solution model of polystyrene in cyclohexane at theta temperature (the red and yellow balls represent carbon and hydrogen atoms, respectively. The cyclohexane molecules are illustrated in line style in the box), (b) the electrostatic potential field around an optimized structure containing two cyclohexane molecules, and (c) around the sole cyclohexane molecule and polystyrene with two repeating units (carbon and hydrogen atoms are represented in green and yellow, respectively).

A molecular simulation study on the adhesion behavior of a functionalized polyethylene-functionalized graphene interface.

Molecular dynamics simulations were applied to investigate interfacial adhesion between functionalized polyethylene (fPE) and functionalized graphene (fG) surfaces. In order to functionalize the PE and graphene surfaces, various types of functional groups were covalently bonded on the surfaces in a random manner. Adhesion between fPE and fG surfaces was evaluated by the calculation of work of separation (Wsep), while the interfaces were not allowed to relax. According to the simulation results, the combination of the atomic roughness effect and the electronic properties of the functional groups had influence on the adhesion between PE and graphene. The effect of surface reorganization was also investigated by devoting sufficient time for relaxation of the interface. The adhesion in the relaxed interfaces was evaluated via the work of adhesion (Wadh). Relaxation of the interface caused to decrease the atomic roughness of the PE surface, which enhanced adhesion in all of the systems compared to their unrelaxed models. In addition to surface flattening, relaxation also brought about an increase in the atomic density at the interface, which led to enhance the van der Waals interaction and increase interfacial adhesion.