Drug delivery from a ring implant attached to intraocular lens: An in-silico investigation.

Multiple iterations required to design ocular implants, which will last for the desired operational period of months or even years, necessitate the use of in-silico models for ocular drug delivery. In this study, we developed an in-silico model to simulate the flow of Aqueous Humor (AH) and drug delivery from an implant to the Trabecular Meshwork (TM). The implant, attached to the side of the intraocular lens (IOL), and the TM are treated as porous media, with their effects on AH flow accounted for using the Darcy equation.

Theory and simulations of light-induced self-assembly in colloids with quantum chemistry derived empirical potentials.

Light-induced self-assembly (LISA) is a non-invasive method for tuning material properties. Photoresponsive ligands coated on the surfaces of nanoparticles are often used to achieve LISA. We report simulation studies for a photoresponsive ligand, azobenzene dithiol (ADT), which switches from a -to- configuration on exposure to ultraviolet light, allowing self-assembly in ADT-coated gold nanoparticles (NPs).

Hydrogen-Bonded Fibrous Nanotubes Assembled from Trigonal Prismatic Building Blocks.

In reticular chemistry, molecular building blocks are designed to create crystalline open frameworks. A key principle of reticular chemistry is that the most symmetrical networks are the likely outcomes of reactions, particularly when highly symmetrical building blocks are involved. The strategy of synthesizing low-dimensional networks aims to reduce explicitly the symmetry of the molecular building blocks.

Monte Carlo simulations of spherocylinders interacting with site-dependent square-well potentials.

Monte Carlo simulations are performed to study the self-assembly of a dilute system of spherocylinders interacting with square-well potential. The interactions are defined between randomly placed sites on the axis of the spherocylinder, akin to the interacting groups on a rigid rodlike molecule. This model therefore also serves as a minimal coarse-grained representation of a system of low molecular weight or stiff polymers with contour lengths significantly lower than the persistence length, interacting predominantly with short-range interactions (e.

Study of the Glycerol Hydrogenolysis Reaction on Cu, Cu-Zn, and Cu-ZnO Clusters.

Quantum chemistry calculations have been performed to access the efficacy of Cu-based catalysts in various mechanistic steps of the glycerol hydrogenolysis reaction. Calculations are first performed for reactants in the gas phase (noncatalyzed system) and reactants in the gas phase with a 3-atom Cu cluster (catalyzed system). We demonstrate that the glycerol to ethylene glycol conversion is preferred in the noncatalyzed system but glycerol conversion to 1,2-propanediol via the 2-acetol intermediate is preferred in the catalyzed system.

Studying Drug Release through Polymeric Controlled Release Formulations in United States Pharmacopoeia 2 Apparatus Using Multiphysics Simulation and Experiments.

In vitro dissolution of oral drug formulations is often studied using the United States Pharmacopoeia (USP) apparatus. Although a well-stirred vessel or a perfect sink assumption is often employed in the modeling of in vitro dissolution in USP apparatus, such a limit is usually not realized in actual experimental conditions. The interplay of hydrodynamics in the vessel and the swelling and erosion of dosage forms often results in substantial deviations from the dissolution behavior obtained under perfect sink approximation.

Experiments and modeling of controlled release behavior of commercial and model polymer-drug formulations using dialysis membrane method.

Standard dissolution testing methods typically do not correlate strongly with the in vivo drug release behavior for the oral delivery products, since they only focus on the drug dissolution in the gastric/intestinal fluid and do not account for the intestinal absorption of drug. Artificial gastrointestinal systems attempt to bridge this gap by using dialysis membranes as a proxy for the intestinal membranes. We present a systematic proof-of-concept study of how the drug dissolution and drug absorption are mimicked in such systems for the case of polymer-drug formulations.

Effect of size and charge asymmetry on aggregation kinetics of oppositely charged nanoparticles.

We report a theoretical and experimental study of the aggregation kinetics of oppositely charged nanoparticles. Kinetic Monte Carlo simulations are performed for symmetric, charge-asymmetric and size-asymmetric systems of oppositely charged nanoparticles. Simulation results show that both the weight and number average aggregate size kinetics exhibit power law scaling with different exponents for small and intermediate time of evolution.

Molecular Insights into the Effects of Media-Drug and Carrier-Drug Interactions on pH-Responsive Drug Carriers.

We have performed two sets of all atom molecular dynamics (MD) simulations of poly(acrylic acid) (PAA) oligomers, considered as a model pH-responsive drug carrier. In the first set, multiple oligomers of PAA are simulated in model gastric and intestinal fluids, where the degree of deprotonation of PAA oligomers is varied with the medium pH. Since the gastric fluid has a pH substantially lower than that of intestinal fluid, PAA is relatively lesser ionized in gastric fluid and forms aggregates.

Mathematical Models for Controlled Drug Release Through pH-Responsive Polymeric Hydrogels.

Hydrogels consisting of weakly charged acidic/basic groups are ideal candidates for carriers in oral delivery, as they swell in response to pH changes in the gastrointestinal tract, resulting in drug entrapment at low pH conditions of the stomach and drug release at high pH conditions of the intestine. We have developed 1-dimensional mathematical models to study the drug release behavior through pH-responsive hydrogels. Models are developed for 3 different cases that vary in the level of rigor, which together can be applied to predict both in vitro (drug release from carrier) and in vivo (drug concentration in the plasma) behavior of hydrogel-drug formulations.

Assessing the efficiency of polymeric excipients by atomistic molecular dynamics simulations.

We have performed all-atom molecular dynamics simulations of aqueous solutions of model oligomers of hydroxypropyl methylcellulose (HPMC) and hydroxypropyl methylcellulose acetate succinate (HPMCAS) excipients interacting with a representative poorly soluble active pharmaceutical ingredient (API), phenytoin. Simulations reveal formation of excipient-API complexes for some of the oligomers, which results in a reduction of API aggregation. API aggregation and diffusivity decreased with an increase in excipient content.

Kinetic Monte Carlo Simulations of Flow-Assisted Polymerization.

We performed kinetic Monte Carlo simulations on a model of a polymerization process in the presence of a periodic oscillatory flow to explore the role of mixing in polymerization reactors. Application of an oscillatory flow field helps overcome the diffusive limitations that develop during a polymerization process due to an increase in the molecular weights of polymer chains, thereby giving rise to high rates of polymerization. A systematic increase in the flow strength results in a "dynamic" coil-stretch transition, leading to an elongation of polymer chains.

A practical integral equation for the structure and thermodynamics of hard sphere Coulomb fluids.

A closure for the Ornstein-Zernike equation is presented, applicable for fluids of charged, hard spheres. From an exact, but intractable closure, we derive the radial distribution function of nonlinearized Debye-Hückel theory by subsequent approximations, and use the information to formulate a new closure by an extension of the mean spherical approximation. The radial distribution functions of the new closure, coined Debye-Hückel-extended mean spherical approximation, are in excellent agreement with those resulting from the hyper-netted chain approximation and molecular dynamics simulations, in the regime where the latter are applicable, except for moderately dilute systems at low temperatures where the structure agrees at most qualitatively.

A Graphics Processing Unit Implementation of Coulomb Interaction in Molecular Dynamics.

We report a GPU implementation in HOOMD Blue of long-range electrostatic interactions based on the orientation-averaged Ewald sum scheme, introduced by Yakub and Ronchi (J. Chem. Phys.