Kharlampieva Research Group

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    The University of Alabama at Birmingham, Department of Chemistry
    901 14th Street South CHEM273, Birmingham, AL 35294

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Research Projects
Immunomodulatory coatings for cell transplantation
islets_web This project is focused on the development of a novel type of multifunctional cytoprotective material for coating living pancreatic islets. Though transplantation of pancreatic islet cells has emerged as a promising treatment for Type 1 diabetes, its clinical application remains limited due to a number of limitations including both pathogenic innate and adaptive immune responses. The coatings being designed and developed in our laboratory utilize hydrogen-bonded interactions of a natural polyphenol (tannic acid) with poly(N-vinylpyrrolidone) or poly(N-vinylcaprolactam) deposited on the islet surfaces via nonionic layer-by-layer assembly. The developed material combines high chemical stability under physiological conditions with capability of suppressing cytokine synthesis, crucial parameters for prolonged islet integrity, viability, and function in vivo. This type of ultrathin multilayer coating offers new opportunities in the area of advanced multifunctional materials to be used for a cell-based transplantation therapy.
Surface multilayer hydrogels
NR_hydrogels_web This project examines the internal architectures of pH- and temperature- responsive multilayer hydrogels through the exploration of the stratification of polymer layers within the matrices.  Thin surface-attached multilayer hydrogels of stimuli-responsive polymers are attractive candidates for applications in sensing, actuation, and controlled delivery.  We are developing novel synthetic assembly strategies with special emphasis on nanostructured stimuli-responsive ultrathin hydrogels.  The hydrogels are produced in a stepwise assembly of polymers at surfaces.  The effects of cross-linking paths, polymer molecular weight, chemical composition, and pH- and temperature-triggered volume changes on hydrogel architectures are examined.  The project requires comprehensive analyses using unique in situ experimental techniques: structural investigations with neutron reflectometry, compositional analyses with ATR-FTIR, evolution of swelling with in situ ellipsometry, and studies of hydrogel morphology with AFM.
Stimuli-responsive shape transitions in multilayer hydrogel capsules
pH_cubes_web In this project, a new class of shape-changing materials based on ultrathin hollow microparticles (capsules) of specific shape is being developed.  The capsule wall is comprised of a stimuli-sensitive polyelectrolyte hydrogel and is formed using a multilayer approach. The capsules are being designed to reversibly change geometry in response to environmental stimuli (pH, T) with the shape-switchable mechanism controlled at the molecular level. Two types of pH-triggered shape response in cubical hollow microcapsules have been developed. The cubical microcontainers are produced as hydrogel replicas of cubical inorganic microparticles by chemically cross-linking multilayers of hydrogen-bonded coatings.  While cubical single-component capsules turn into spherical-like when transitioned from acidic to neutral pH, cubical two-component hydrogel capsules retain their cubical shape and increased in size.
PVCL_web Thermosensitive multilayer hydrogel films and capsules with a distinct and highly reversible thermoresponsive behavior have also been developed. The cubical temperature-responsive hydrogel capsules shrink upon temperature increase while retaining their cubical shape.  The hydrogels are derived from hydrogen-bonded multilayers through chemical cross-linking of the copolymer layers.  The degree of hydrogel temperature-triggered shrinkage can be controlled by varying the cross-link density by ranging the amount of cross-linkable groups in the copolymer chains. Since the dynamic control over materials shape plays a key role in the complex biological environment and is important in engineering science and medicine, the project findings can provide new prospects for developing polymeric materials with predictable shape and size-changing properties for controlled delivery and shape-regulated cellular uptake.
Nanocapsule carriers for ultrasound-induced local delivery
DOX_loaded_web The major focus of this research is to develop novel polymer-based nanostructured carriers for delivery of anticancer drugs using ultrasound for targeting delivery. Oncology is a field of medicine for which there has been a remarkable contribution from nanotechnology. One of the most challenging problems still remains unresolved is controlled delivery of therapeutics to solid tumors. The project focuses on development of approaches for encapsulating anticancer drugs or viral agents within microcapsule carriers for controlled delivery to tumors. Biocompatible and biodegradable microcapsules consisting of open submicron-size cavity and ultrathin polymeric shell are being synthesized and utilized as carriers.  The release efficacy is assessed in cancer cell cultures using microscopy and flow cytometry. Left: CLSM and SEM images of DOX-loaded capsules.
Multilayer capsules for shape-controlled cellular uptake
Silk_HB_web This project focuses on the development of the multilayer micro- and nanocapsules (nanovectors) of non-spherical shape for controlled cellular uptake.  In nature, each shape evolved for specific physiological reasons. Non-spherical shape and elasticity are the physical characteristics responsible for ability of cells to overcome transport barriers en route to the target lesion, which are universal for cells transported in the blood stream. The shape of erythrocytes guarantees the optimal surface-to-volume ratio that is necessary for margination in the blood and enabling the delivery of oxygen from hemoglobin to the outside tissues. The extraordinary flexibility of mammalian erythrocytes enables them to deform in the circulation as they pass through restrictions in the vasculature that is smaller than their diameter. We design cell-mimicking nanovectors possessing the characteristics of elasticity and responsiveness to pH gradients in tumor microenvironment. The layer-by-layer assembly of biocompatible and pH- sensitive polymers is used to produce capsules with cell-mimicking shapes.  The effect of capsule shape and elasticity on the interaction with cells present in the circulation and tumor microenvironment are being explored in comparison to their rigid counterparts.  Left: Confocal laser scanning microscopy images of hollow shaped polymer capsules of silk fibroin protein LbL-assembled with polyvinylcaprolactam via hydrogen bonding. 

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