(6dj) Applied Mechanics Studies of Complex Fluids for Pharmacokinetic Application

My research interest lies primarily in non-Newtonian fluid’s behavior in response to external field in bulk and near wall. A considerable portion of earlier research work addressed problems related to modeling response of colloidal hybrids, effect of surface charge and contact mechanics, and capillary sintering during drying of colloidal dispersion. My current research involves development of next generation pharmacokinetic models for therapeutic targeted drug delivery.

A class of hybrid complex fluids is made of colloid hard-core with polymer brushes. For battery research they are used for ion transportation. For gas absorption purposes they act as porous support to screen molecules and hold active absorption agents. In drug delivery hybrid complex fluids (which we refer to as nanogels or deformable nanocarriers) are used as vehicles to carry important drugs and target them to specific tissues that are either inflamed or diseased. In this case the core is made of native proteins such as lysozyme and the brush is made out of biocompatible polymers such as dextran or hyaluronic acid. The dimensions of these nanostructures range from 10-100 nm, which puts them below the diffraction limit, making experimental investigations challenging.

Novel Materials for Targeted Drug Delivery: The deformable nanocarrier has a large molecular weight (10²-10⁵kDa) and it is difficult to predict its structural dynamics using molecular dynamics techniques. There is also a lack of mechanistic insight to predict selectivity of binding of the nanogels to inflamed or diseased tissue under physiologically relevant conditions in vasculature. In order to model the deformable gel-based NC, the structure of the deformable gel is coarse-grained based on theoretical models from polymer physics and simulated annealing protocol, which mimics the experimental method of synthesis of this novel material. The Brownian dynamics framework is incorporated to include hydrodynamic interactions, which led to the calculation of equilibrium and steady-shear rheological properties of the nanogel. Brownian dynamics with near-wall interactions along with rheological response in bulk gives important insight that is essential for drug design and predicts the targeting capabilities to specific tissues, which is important for clinical translation.

Novel Materials for Energy Applications: Nano organic hybrid materials are made of silica cores and polyethylene glycol (PEG) brushes. Most of the applications like flow in a semi-confined space is related to complex flows. Primary goal of my research work has been understanding the properties of these materials at Brownian and mesoscale level by developing theoretical model to characterize these complex materials. Based on these models the steady shear rheological properties and transient response¹ have been investigated. A constitutive model for complex flows exhibiting a variety of local linear flows is derived and applied to a complex stochastically varying flow of the fluid through fixed bed of fibers. If the ratio of size of the core to polymer brushes decreases, the structural anisotropy increases and the material shows sign of strain thinning. Such material acts as an additive, which reduces the internal stresses of the fluid in a conduit and the risk of fracturing of underground pipelines (which is a common problem in fracking process) reduces.

Prior research work was primarily on consolidation and cracking in drying colloidal dispersion. The work addressed fundamental understanding related to colloidal films formation broadly desiccation processes of water-soluble colloids. Water-soluble colloids are important ingredient in paint industry (for reduction of volatile organic components) and for continuous manufacturing of drugs in pharmaceutical processing. Drying of water-soluble colloids and its film formation were investigated through experiments and theory. If a dispersion of colloidal particle is allowed to dry, particles packing under a convective field (set by the evaporation) is in compression and the solvent from bulk, pass through porous bed of particles to reach the interface. Charge nature of the particles changes the conventional drying-consolidation profile³ while the presence of flaws in the packed region is effected due to an interplay between strain energy, stored in the particle network, and interfacial energy.² Experiments were performed in rheometer (semi-confined geometry^4,6) and in microchannels (confined geometry⁵). In semiconfined geometry the pressure required to open a crack from flaw was predicted while in confined geometry the additional effect, due to presence of boundaries and channels, were investigated and hence depicted an overall consolidation behavior.

My research experience is mainly in applied mechanics studies of complex fluids. I would like to further extend the methodologies developed for amphiphilic carriers such as rodlike micelles⁷ to include wall-effects and resolve internal and inhomogeneous / anisotropic stresses-strains near wall. In biomedical applications, rodlike micelles can have long circulating times, which are essential in sustained delivery of drugs required for some medical conditions. Rodlike micelles can also be an important self-assembly for drag reduction in oil pipelines and hot water transportation lines. I plan to carry out experiments in 4-roll mill to understand the response of rodlike micelles in a variety of flows and extend the present understanding of soft glassy fluid elements to rodlike micelles, in general FENE dumbbells. I am also interested in packing and sintering of alumina film  formation with or without a heat source. Alumina is widely used as refractory coatings, catalyst and more recently transparent optics. I would like to study alumina film formation through theory and experiments to predict packing and its effect on film properties.

I wish to acknowledge funding support for my work through Cornell University-KAUST center and NIH 1R01EB006818-05 & NIH U01-EB016027, made available to me through my postdoctoral supervisors.

References

1. Sarkar, A. and D. L. Koch, “Brownian dynamics simulations of a local-fluid-volume preserving model of solvent-free nanoparticle fluids,” The Society of Rheology 84th Annual Meeting (2013).
2. Sarkar, A. and M. S. Tirumkudulu, “Asymptotic analysis of stresses near a crack tip in a two- dimensional colloidal packing saturated with liquid,” Phys. Rev. E, 83, 051401 (2011).
3. Sarkar, A. and M. S. Tirumkudulu, “Consolidation of charged colloids during drying,” Langmuir, 25(9), 4945–4953 (2009).
4. Sarkar, A. and M. S. Tirumkudulu, “Critical stress required to open a flaw in a two dimensional colloidal packing saturated with solvent,” International Symposium on Recent and Emergent Advances in Chemical Engineering (REACH).
5. Sarkar, A. and M. S. Tirumkudulu, “Delamination of drying nanoparticle suspensions,” Soft Matter, 7, 8816–8822 (2011).
6. Sarkar, A. and M. S. Tirumkudulu, “Ultimate strength of a colloidal packing,” Soft Matter, 8, 303–306 (2012).
7. Discher Dennis E. and Eisenberg Adi,"Polymer Vesicles", Science 297, 967 (2002).