Polymer Science Commons^™

Towards The Rational Design And Application Of Polymers For Gene Therapy: Internalization And Intracellular Fate, Landon Alexander Mott

Theses and Dissertations--Chemical and Materials Engineering

Gene therapy is an approach for the treatment of acquired cancers, infectious disease, degenerative disease, and inherited genetic indications. Developments in the fields of immunotherapies and CRISPR/Cas9 genome editing are revitalizing the efforts to move gene therapy to the forefront of modern medicine. However, slow progress and poor clinical outcomes have plagued the field due to regulatory and safety concerns associated with the flagship delivery vector, the recombinant virus. Immunogenicity and poor transduction in certain cell types severely limits the utility of viruses as a delivery agent of nucleic acids. As a result, significant efforts are being made to develop …

Comparison Of Eosin And Fluorescein Conjugates For The Photoinitiation Of Cell-Compatible Polymer Coatings, Jacob L. Lilly, Anuhya Gottipati, Calvin F. Cahall, Mohamed Agoub, Brad J. Berron

Chemical and Materials Engineering Faculty Publications

Targeted photopolymerization is the basis for multiple diagnostic and cell encapsulation technologies. While eosin is used in conjunction with tertiary amines as a water-soluble photoinitiation system, eosin is not widely sold as a conjugate with antibodies and other targeting biomolecules. Here we evaluate the utility of fluorescein-labeled bioconjugates to photopolymerize targeted coatings on live cells. We show that although fluorescein conjugates absorb approximately 50% less light energy than eosin in matched photopolymerization experiments using a 530 nm LED lamp, appreciable polymer thicknesses can still be formed in cell compatible environments with fluorescein photosensitization. At low photoinitiator density, eosin allows more …

Surface Functionalization Via Photoinitiated Radical Polymerization For Rare Cell Isolation And Mechanical Protection, Calvin Frank Cahall

Theses and Dissertations--Chemical and Materials Engineering

Surface functionalization of living cells for cell therapeutics has gained substantial momentum in the last two decades. From encapsulating islets of Langerhans, to cell laden gels for tissue scaffolds, to individual cell encapsulation in thin hydrogels, to surface adhesives and inert surface camouflage, modification of living cell surfaces has a wide array of important applications. Here we use hydrogel encapsulation of individual cells as a mode of protection from mechanical forces for high throughput cell printing, and chemical stimuli for the isolation of rare cells in blood.

In the first study, we review methods of surface functionalization and establish a …

Synthesis And Characterization Of Poly(Simvastatin) - Incorporated Copolymers And Blends For Bone Regeneration, Theodora Asafo-Adjei

Theses and Dissertations--Biomedical Engineering

Common biodegradable polyesters such as poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA) and poly(ε-caprolactone) (PCL) are used as drug delivery vehicles for tissue regenerative applications. However, they are typically bioinert, with drug loading limitations. Polymerizing the active agent or precursor into its respective biodegradable polymer would control drug loading via molar ratios of drug to initiator used for synthesis. Simvastatin was chosen due to its favorable anti-inflammatory, angiogenic, and osteogenic properties. In addition, its lactone ring lends itself to ring-opening polymerization and, consequently, the synthesis of poly(simvastatin) with controlled simvastatin release.

Simvastatin was first polymerized with a 5kDa methyl-terminated poly(ethylene glycol) …

Surface-Initiated Polymerizations For The Rapid Sorting Of Rare Cancer Cells, Jacob L. Lilly

Theses and Dissertations--Chemical and Materials Engineering

Cancer metastasis directly accounts for an estimated 90% of all cancer related deaths and is correlated with the presence of malignant cells in systemic circulation. This observed relationship has prompted efforts to develop a fluid biopsy, with the goal of detecting these rare cells in patient peripheral blood as surrogate markers for metastatic disease as a partial replacement or supplement to tissue biopsies. Numerous platforms have been designed, yet these have generally failed to support a reliable fluid biopsy due to poor performance parameters such as low throughput, low purity of enriched antigen positive cells, and insufficiently low detection thresholds …

Synthesis And Characterization Of Curcumin Polymer For Application In Radiation Induced Lung Damage, Mark C. Bailey

Theses and Dissertations--Chemical and Materials Engineering

Radiotherapy is used as a primary treatment for many cancers, including lung cancer. Although radiotherapy has proven to be an effective cancer treatment, its use is heavily limited due to the peripheral toxicity to healthy tissue. In this work, the antioxidant, curcumin, was tested as a radioprotectant to reduce radiation damage to healthy cells. Curcumin has been limited in use due to its poor bioavailability. In order to avoid problems associated with free curcumin delivery, curcumin poly(beta-amino ester) (CPBAE) was synthesized.

The first study investigated the in vitro radioprotection effect of curcumin in HUVEC dosed with gamma radiation. Cells treated …

Bioactive Poly(Beta-Amino Ester) Biomaterials For Treatment Of Infection And Oxidative Stress, Andrew L. Lakes

Theses and Dissertations--Chemical and Materials Engineering

Polymers have deep roots as drug delivery tools, and are widely used in clinical to private settings. Currently, however, numerous traditional therapies exist which may be improved through use of polymeric biomaterials. Through our work with infectious and oxidative stress disease prevention and treatment, we aimed to develop application driven, enhanced therapies utilizing new classes of polymers synthesized in-house. Applying biodegradable poly(β-amino ester) (PBAE) polymers, covalent-addition of bioactive substrates to these PBAEs avoided certain pitfalls of free-loaded and non-degradable drug delivery systems. Further, through variation of polymer ingredients and conditions, we were able to tune degradation rates, release profiles, cellular …

Synthesis And Characterization Of Antioxidant Conjugated Poly(Βeta-Amino Ester) Micro/Nanogels For The Suppression Of Oxidative Stress, Prachi Gupta

Theses and Dissertations--Chemical and Materials Engineering

Oxidative stress is a pathophysiological condition defined by an increased production of reactive oxygen species (ROS), which can result in the growth arrest of cells followed by cell disintegration or necrosis. A number of small molecule antioxidants (e.g. curcumin, quercetin and resveratrol) are capable of directly scavenging ROS, thereby short-circuiting the self-propagating oxidative stress state. However, poor solubility and rapid 1^st pass metabolism results in overall low bioavailability and acts as a barrier for its use as a drug to suppress oxidative stress efficiently.

To overcome this limitation, these small molecule antioxidants were covalently conjugated into poly(β-amino ester) (PβAE) …

Biomimetic Oral Mucin From Polymer Micelle Networks, Sundar Prasanth Authimoolam

Theses and Dissertations--Chemical and Materials Engineering

Mucin networks are formed by the complexation of bottlebrush-like mucin glycoprotein with other small molecule glycoproteins. These glycoproteins create nanoscale strands that then arrange into a nanoporous mesh. These networks play an important role in ensuring surface hydration, lubricity and barrier protection. In order to understand the functional behavior in mucin networks, it is important to decouple their chemical and physical effects responsible for generating the fundamental property-function relationship. To achieve this goal, we propose to develop a synthetic biomimetic mucin using a layer-by-layer (LBL) deposition approach. In this work, a hierarchical 3-dimensional structures resembling natural mucin networks was generated …

Inhalable Nanocomposites And Anticancer Agents For Cancer Therapy, Nathanael A. Stocke

Theses and Dissertations--Chemical and Materials Engineering

Cancer is designated as the leading cause of mortality worldwide and lung cancer is responsible for nearly 30% of all cancer related deaths. Over the last few decades mortality rates have only marginally increased and rates of recurrence remain high. These factors, among others, suggest the need for more innovative treatment modalities in lung cancer therapy. Targeted pulmonary delivery is well established for treating pulmonary diseases such as asthma and provides a promising platform for lung cancer therapy. Increasing local deposition of anticancer agents (ACAs) and reducing systemic exposure of these toxic moieties could lead to better therapeutic outcomes and …

Applications Of Antioxidant And Anti-Inflammatory Polymers To Inhibit Injury And Disease, David B. Cochran

Theses and Dissertations--Chemical and Materials Engineering

There is an undeniable link between oxidative stress, inflammation, and disease. Currently, approaches using antioxidant therapies have been largely unsuccessful due to poor delivery and bioavailability. Responding to these limitations, we have developed classes of polymer and delivery systems that can overcome the challenges of antioxidant and anti-inflammatory therapy. In our initial studies, nanoparticles of poly(trolox), a polymeric form of trolox, were surface-modified with antibodies. This modification allows for specific targeting to endothelial cells, affording controllable and localized protection against oxidative stress. We have shown these targeted nanoparticles bind, internalize, and provide protection against oxidative stress generation and cytotoxicity from …