Diffusion of curcumin in PLGA-based carriers for drug delivery: a molecular dynamics study.

CONTEXT: The rapid growth and diversification of drug delivery systems have been significantly supported by advancements in micro- and nano-technologies, alongside the adoption of biodegradable polymeric materials like poly(lactic-co-glycolic acid) (PLGA) as microcarriers. These developments aim to reduce toxicity and enhance target specificity in drug delivery. The use of in silico methods, particularly molecular dynamics (MD) simulations, has emerged as a pivotal tool for predicting the dynamics of species within these systems. This approach aids in investigating drug delivery mechanisms, thereby reducing the costs associated with design and prototyping. In this study, we focus on elucidating the diffusion mechanisms in curcumin-loaded PLGA particles, which are critical for optimizing drug release and efficacy in therapeutic applications. METHODS: We utilized MD to explore the diffusion behavior of curcumin in PLGA drug delivery systems. The simulations, executed with GROMACS, modeled curcumin molecules in a representative volume element of PLGA chains and water, referencing molecular structures from the Protein Data Bank and employing the CHARMM force field. We generated PLGA chains of varying lengths using the Polymer Modeler tool and arranged them in a bulk-like environment with Packmol. The simulation protocol included steps for energy minimization, T and p equilibration, and calculation of the isotropic diffusion coefficient from the mean square displacement. The Taguchi method was applied to assess the effects of hydration level, PLGA chain length, and density on diffusion. RESULTS: Our results provide insight into the influence of PLGA chain length, hydration level, and polymer density on the diffusion coefficient of curcumin, offering a mechanistic understanding for the design of efficient drug delivery systems. The sensitivity analysis obtained through the Taguchi method identified hydration level and PLGA density as the most significant input parameters affecting curcumin diffusion, while the effect of PLGA chain length was negligible within the simulated range. We provided a regression equation capable to accurately fit MD results. The regression equation suggests that increases in hydration level and PLGA density result in a decrease in the diffusion coefficient.

Method for predicting the wettability of micro-structured surfaces by continuum phase-field modelling.

Numerical prediction of material properties is attracting the attention of the scientific community and industry because of its usefulness in the design process. In the fields of fluid dynamics and microfluidics, several simulation methods have been proposed and adopted to evaluate the properties of surfaces and material interfaces, thanks to the increasing computational power available. However, despite the efforts made, a general and standardized methodology for implementing such methods is still lacking, thus requiring a trial-and-error approach for each new problem, making them difficult to implement and creating a bottleneck at the initial stage of surface design. Here, we report a validated protocol to evaluate the wettability of micro-structured surfaces with a phase-field model. Summarizing:•Simulating physical phenomena with multi-phase flows and moving contact lines can be a challenging task, due to the coupling among disparate length scales.•Using the Cahn-Hilliard diffuse-interface model, moving contact lines can be extensively investigated, although difficulties may arise when implementing numerical simulations, e.g., model parameter calibration, selection of boundary conditions, post-processing of fluid dynamics/equilibrium.•A method for employing this model and evaluating the physical consistency of the results is proposed here, considering the wettability of micro-structured surfaces as a case study.

A new methodology for measuring solid/liquid interfacial energy.

HYPOTHESIS: The interfacial energy γsl between a solid and a liquid designates the affinity between these two phases, and in turn, the macroscopic wettability of the surface by the fluid. This property is needed for precise control of fluid-transport phenomena that affect the operation/quality of commercial devices/products. Although several indirect or theoretical approaches can quantify the solid/liquid interfacial energy, no direct experimental procedure exists to measure this property for realistic (i.e. rough) surfaces. Makkonen hypothesized that the frictional resistance force per unit contact-line length is equal to the interfacial energy on smooth surfaces, which, however, are rarely found in practice. Consequently, the hypothesis that Makkonen's assumption may also hold for rough surfaces (which are far more common in practice) arises naturally. If so, a reliable and simple experimental methodology of obtaining γsl for rough surfaces can be put forth. This is accomplished by performing dynamic contact-angle experiments on rough surfaces that quantify the relationship between the frictional resistance force per unit contact-line length acting on an advancing liquid (Fp,a) and the surface roughness in wetting configurations. EXPERIMENT: We perform static and advancing contact-line experiments with aqueous and organic liquids on different hydrophilic surfaces (Al, Cu, Si) with varying Wenzel roughnesses in the range 1-2. These parameters are combined with the liquid's known surface tension to determine Fp,a. FINDINGS: Fp,a rises linearly with the surface roughness. Analysis based on existing theories of wetting and contact-angle hysteresis reveals that the slope of Fp,a vs.Wenzel roughness is equal to the solid/liquid interfacial energy, which is thus determined experimentally with the present measurements. Interfacial energies obtained with this experimental approach are within 12% of theoretically predicted values for several solid/liquid pairs, thereby validating this methodology.

Ultrafast nano generation of acoustic waves in water via a single carbon nanotube.

Generation of ultra high frequency acoustic waves in water is key to nano resolution sensing, acoustic imaging and theranostics. In this context water immersed carbon nanotubes (CNTs) may act as an ideal optoacoustic source, due to their nanometric radial dimensions, peculiar thermal properties and broad band optical absorption. The generation mechanism of acoustic waves in water, upon excitation of both a single-wall (SW) and a multi-wall (MW) CNT with laser pulses of temporal width ranging from 5 ns down to ps, is theoretically investigated via a multiscale approach. We show that, depending on the combination of CNT size and laser pulse duration, the CNT can act as a thermophone or a mechanophone. As a thermophone, the CNT acts as a nanoheater for the surrounding water, which, upon thermal expansion, launches the pressure wave. As a mechanophone, the CNT acts as a nanopiston, its thermal expansion directly triggering the pressure wave in water. Activation of the mechanophone effect is sought to trigger few nanometers wavelength sound waves in water, matching the CNT acoustic frequencies. This is at variance with respect to the commonly addressed case of water-immersed single metallic nano-objects excited with ns laser pulses, where only the thermophone effect significantly contributes. The present findings might be of impact in fields ranging from nanoscale non-destructive testing to water dynamics at the meso to nanoscale.

Anisotropic Electrostatic Interactions in Coarse-Grained Water Models to Enhance the Accuracy and Speed-Up Factor of Mesoscopic Simulations.

Water models with realistic physical-chemical properties are essential to study a variety of biomedical processes or engineering technologies involving molecules or nanomaterials. Atomistic models of water are constrained by the feasible computational capacity, but calibrated coarse-grained (CG) ones can go beyond these limits. Here, we compare three popular atomistic water models with their corresponding CG model built using finite-size particles such as ellipsoids. Differently from previous approaches, short-range interactions are accounted for with the generalized Gay-Berne potential, while electrostatic and long-range interactions are computed from virtual charges inside the ellipsoids. Such an approach leads to a quantitative agreement between the original atomistic models and their CG counterparts. Results show that a timestep of up to 10 fs can be achieved to integrate the equations of motion without significant degradation of the physical observables extracted from the computed trajectories, thus unlocking a significant acceleration of water-based mesoscopic simulations at a given accuracy.

Effects of Graphene Oxidation on Interaction Energy and Interfacial Thermal Conductivity of Polymer Nanocomposite: A Molecular Dynamics Approach.

Interfacial characteristics of polymer nanocomposites represent a crucial aspect to understand their global properties and to evaluate the interaction between nanofillers and matrix. In this work we used a molecular dynamics (MD) approach to characterize the interfacial region at the atomistic scale of graphene-based polymer nanocomposites. Three different polymer matrixes were considered, polylactic acid (PLA), polypropylene (PP) and epoxy resin (EPO), which were reinforced with three types of graphene fillers: pristine graphene (G), graphene oxide (GO) and reduced graphene oxide (rGO). In particular, the compatibility of the nanofillers in polymer matrixes were evaluated in terms of the interaction energy, while the interfacial thermal resistance (Kapitza resistance) between matrices and fillers was calculated with a nonequilibrium molecular dynamics (NEMD) method. Results showed that the oxidation degree plays an important role on the studied properties of the interfacial region. In particular, it was observed that the Kapitza resistance is decreased in the oxidized graphene (GO and rGO), while interaction energy depended on the polarity of the polymer matrix molecules and the contribution of the Coulombic component.