Sanat Mohanty

Multiscale simulation methods for nanomaterials

1. Overview of Multi-Scale Simulation Methods for Materials (Sanat S. Mohanty and Richard B. Ross). 2. Influence of Water and Fatty Acid Molecules on Quantum Photoinduced Electron Tunneling in Self-Assembled Photosynthetic Centers of Minimal Protocells (A. Tamulis, V. Tamulis, H. Ziock, and S. Rasmussen). 3. Optimizing the Electronic Properties of Carbon Nanotubes using Amphoteric Doping (Bob G. Sumpter and Vincent Meunier). 4. Using Order and Nanoconfinement to Tailor Semiconducting Polymers - A Combined Experimental and Multiscale Computational Study (Michael L. Drummond, Bob G. Sumpter, Michael D. Barnes, William A. Shelton, Jr., and Robert J. Harrison). 5. Coarse Grain to Atomistic Mapping Algorithm: A Tool for Multiscale Simulations (Steven O. Nielsen, Bernd Ensing, Preston B. Moore, and Michael L. Klein). 6. Microscopic Insights into the Dynamics of Protein-Solvent Mixtures (Taner E. Dirama and Gustavo A. Carri). 7. Mesoscale Simulations of Surface Modified Nanospheres in Solvents (Sanat Mohanty). 8. Fixing Interatomic Potentials Using Multiscale Modeling: ad hoc Schemes for Coupling Atomic and Continuum Simulations (Clifford W. Padgett, J. David Schall, J. Wesley Crill, and Donald W. Brenner). 9. Fully Analytic Implementation of Density Functional Theory for Efficient Calculations on Large Molecules (Rajendra R. Zope and Brett I. Dunlap). 10. Al Nanoparticles: Accurate Potential Energy Functions and Physical Properties (Nathan E. Schultz, Ahren W. Jasper, Divesh Bhatt, J. Ilja Siepmann, and Donald G. Truhlar). 11. Large-scale Monte Carlo Simulations for Aggregation, Self-Assembly and Phase Equilibria (Jake L. Rafferty, Ling Zhang, Nikolaj D. Zhuravlev, Kelly E. Anderson, Becky L. Eggimann, Matthew J. McGrath, and J. Ilja Siepmann). 12. New QM/MM Models for Multi-scale Simulation of Phosphoryl Transfer Reactions in Solution (Kwangho Nam, Jiali Gao, and Darrin M. York). 13. Modeling the Thermal Decomposition of Large Molecules and Nanostructures (Marc R. Nyden, Stanislav I. Stoliarov, and Vadim D. Knyazev). 14. Predicting Dynamic Mesoscale Structure of Commercially Relevant Surfactant Solutions (Fiona Case).

In vitro controlled release of Rifampicin through liquid-crystalline folate nanoparticles

Rifampicin is one of the frontline drugs for tuberculosis therapy but poor bioavailability of Rifampicin in combination with other anti-tuberculosis drugs is a subject of concern. Nano-based formulations for sustained release of anti-tubercular drugs have been shown to increase antibacterial efficacy and pharmacokinetic behavior. In the present study, liquid-crystalline folate nanoparticles were designed for sustained delivery of Rifampicin and its in vitro release study is reported. Liquid-crystalline nanoparticles of biocompatible folate ions consist of self assembled structures, resulting in high encapsulation, controlled release and low drug losses of about 20-30%, which is significant in itself. This study reports the size-control method of forming Rifampicin encapsulated folate nanoparticles as well as the parameters to control the release profiles of Rifampicin through these nanoparticles. These designs are able to present sustained release for over 25 days. The effect of different parameters such as nanoparticles size, type of cross-linking cation, cross-linking cation concentration and drug-loading on Rifampicin release was studied in vitro. The intracellular uptake and low cytotoxicity of nanoparticles by alveolar macrophages was also demonstrated using fluorescence microscopy and MTT assay respectively.

Predictive modeling of self assembly of chromonics materials

This study identifies mechanisms of self-assembly of a chromonic molecule with interesting self-assembly properties. Results from molecular dynamics (MD) studies used to understand the moieties of the molecule that affect the structure are consistent with experimental observations of these self-assembled structures. Coulombic forces, with significant contributions from π–π interactions drives the self-assembly of this class of materials; hydrogen bond energies are also significant.

Design Considerations for Chemotherapeutic Drug Nanocarriers

The use of nanotechnology in delivering the chemotherapeutics drug has gained much attention recently. It is capable of killing the cancer much more effectively than any other method. The drug delivery systems using nanocarrier significantly enhances the efficacy of drug by improving the pharmacokinetics and the distribution of the drug to specific organs. For designing an effective nanocarrier, an insight of size, shape, surface chemistry and geometry is important. This review gives a map of guidelines for design of nanoparticle based chemotherapy. It reviews the mechanism of delivery in different pathways, physiology and chemistries involved and barriers to transport and delivery of nanocarrier based drugs, specifically for chemotherapeutic drugs. The microenvironment and physiology of a tumor site and its chemical environment is also reviewed, focusing on the impact on delivery. This review is an attempt to map the parameters that will help effective design of nanoparticles as drug carriers for chemotherapeutics. It discusses the accurate designing of nanocarriers as well as the effect of the environment to which a nanocarrier is exposed inside the body, its fate and uptake.

In vitro control release, cytotoxicity assessment and cellular uptake of methotrexate loaded liquid-crystalline folate nanocarrier

Folate molecules self-assemble in the form of stacks to form liquid-crystalline solutions. Nanocarriers from self-assembled folates are composed of highly ordered structures, which offer high encapsulation of drug (95-98%), controlled drug release rates, active cellular uptake and biocompatibility. Recently, we have shown that the release rates of methotrexate can be controlled by varying the size of nanoparticles, cross-linking cation and cross-linking concentration. The present study reports the in vitro cytotoxic behavior of methotrexate loaded liquid-crystalline folate nanoparticles on cultured HeLa cells. Changing drug release rates can influence cytotoxicity of cancer cells. Therefore, to study the correlation of release rate and cytotoxic behavior, the effect of release controlling parameters on HeLa cells was studied through MTT assay. It is reported that by controlling the methotrexate release, the survival rates of HeLa cells can be controlled. Released methotrexate kills HeLa cells as effectively as free methotrexate solution. The co-culture based in vitro cellular uptake study through fluorescence microscopy on folate receptor positive and negative cancer cells shows that the present nanocarrier has the potential to distinguish cancer cells from normal cells. Overall, the present study reports the in vitro performance of self-assembled liquid-crystalline folate nanoparticles, which will be a platform for further in vivo studies and clinical trials.

Effect of Uniformly Applied Force and Molecular Characteristics of a Polymer Chain on Its Adhesion to Graphene Substrates

The force-induced desorption of a polymer chain from a graphene substrate is studied with molecular dynamics (MD). A critical force needs to be exceeded before detachment of the polymer from the substrate. It is found that for a chain to exhibit good adhesive properties the chain configuration should consist of fibrils-elongated, aligned sections of polymers and cavities which dissipate the applied energy. A fibrillation index is defined to quantify the quality of fibrils. We focus on the molecular properties of the polymer chain, which can lead to large amounts of fibrillation, and find that both strong attraction between the polymer and substrate and good solvency conditions are important conditions for this. We also vary the stiffness of the chain and find that for less stiff chains a plateau in the stress-strain curve gives rise to good adhesion however for very stiff chains there is limited elongation of the chain but the chain can still exhibit good fibrillation by a lamella-like rearrangement. Finally, it is found that the detachment time, t, of a polymer from the adsorbed substrate is inversely proportional to force, F (i.e., t ∝ F(-γ)), where exponent γ depends on the solvent quality, polymer-substrate attraction, and chain stiffness.

Why folates self-assemble: a simulation-based study

Folates (and other chromonics molecules) have been shown to self-assemble into ordered structures even at low concentrations. In this study, simulations are used to first replicate the self-assembly of folates and understand why folic acid does not assemble while folate ions do. Subsequently, these simulations replicate the change in structure and behaviour of the assembly with increasing concentration of folates, comparing them to experimental observations in earlier studies. The study then uses fictitious molecules and ions to understand which components of the folate ions drive, or otherwise affect, assembly of the folates and to abstract some guiding principles about structure of chromonics molecules and the impact on assembly. This study shows that while the aromatic rings drive stacking, the hydrophilic groups help solvate and hence control the order of the aromatic stacks, and the 1-ring-diacid moiety controls the orientation of the ions in their plane.

Controlled release of folic acid through liquid-crystalline folate nanoparticles

The present study explores folate nanoparticles as nano-carriers for controlled drug delivery. Cross-linked nanoparticles of liquid crystalline folates are composed of ordered stacks. This paper shows that the folate nanoparticles can be made with less than 5% loss in folate ions. In addition, this study shows that folate nanoparticles can disintegrate in a controlled fashion resulting in controlled release of the folate ions. Release can be controlled by the size of nanoparticles, the extent of cross-linking and the choice of cross-linking cation. The effect of different factors like agitation, pH, and temperature on folate release was also studied. Studies were also carried out to show the effect of release medium and role of ions in the release medium on disruption of folate assembly.

Nanoparticle formulation having ability to control the release of protein for drug delivery application

Controlled release of therapeutic protein is desirable for protein delivery applications. This study discuss about a unique nanomaterial which is capable to provide the protein release in controlled manner. The nanomaterial has been synthesized from folic acid molecules and bovine serum albumin (BSA1) is loaded in these nanoparticles as a model protein. The size distribution of the synthesized folic acid nanoparticles was observed between 200 and 300nm. The release study using high performance liquid chromatography suggests that more than 90% of BSA can be encapsulated in the nanoparticles having BSA loaded up to 19.29mg (57% of folic acid loaded). Release study also reveals that more than 95% of the total folic acid and BSA were released in phosphate buffer saline solution within 48h. Investigation of folic acid release along with BSA release reveals that the particles are formed through folic acid-protein complex. Salt concentration in the release medium and crosslinked cations in the nanoparticles are found to be the key parameters to control the release rate. Thus, folic acid nanoparticles are efficient carrier for protein encapsulation and release in the controlled manner with minimum drug loss.

Chromonics: Reviewing a High-performance Self-assembling Structure

Abstract Chromonics form a class of molecules that self-assemble via mechanisms distinctly different from amphiphiles, showing structure and properties that are significantly different. This is a review of scientific development in understanding the thermodynamics of the assembly as well as the control and engineering of assembled structures along with potential applications driving the develop and key technical challenges that need to be solved for further development.