Browsing by Subject "polymer synthesis"
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Item Development of Model Diblock Copolymer Surfactants for Mechanistic Investigations of Cell Membrane Stabilization(2015-08) Haman, KarenAmphiphilic triblock copolymers of poly(ethylene oxide) and poly(propylene oxide), generically referred to as poloxamers, have been identified for therapeutic use in cell membrane stabilization applications since the early 1990s. Historically, mechanistic investigations of block copolymer facilitated membrane stabilization have nearly exclusively featured poloxamers, commercially available in a wide range of molecular weights and hydrophobic/hydrophilic compositions. This work instead considers diblock copolymers of poly(ethylene oxide) and poly(propylene oxide), for which molecular properties can be easily tuned by living anionic polymerization. The diblock architecture simplifies the structure-function understanding of block copolymer interactions with membranes by eliminating a redundant hydrophilic block (A) from the poloxamer A-B-A architecture. Work presented here indicates that these diblock copolymers are capable of shielding liposome model membranes from harmful free radical-initiated peroxidation at lower loadings than analogous triblock copolymers. Besides the pharmacological advantages of lower required doses, the finding highlights the significance with respect to membrane interaction of differences in the chemical environments of the hydrophobic blocks between the triblock and diblock architectures. From this point, the roles of both hydrophobic block length and end-functionality were explored in liposome and in vitro model stresses, and the dependence of therapeutic benefit on each was established. Future systems to consider are discussed, and additional methods for investigation are detailed.Item Investigating The Interactions Of Polycations With Nucleic Acid And The Mechanisms Of Delivery(2015-05) Sprouse, DustinPolymers - large macromolecules composed from many smaller subunits - have ever-growing uses and potentials in our lives. More specifically, cationically charged polymers have been widely explored as non-viral vectors to deliver nucleic acid to cells in an effort to regulate gene and protein expression. The polymeric vehicle must not only bind and complex with DNA to protect and deliver it to the targeted site, but also efficiently dissociate from the DNA and be non-toxic to the cell or host organism. Herein lies the wide array of polymers that must be rationally designed and synthesized in order for the delivery vehicle to perform its specific function. At the turn of the century, two monumental achievements paved way for gene therapy. First, the Human Genome Project was completed. This milestone continues to unravel important information about the genetic basis of human health, disease, hereditary, and genetic dispositions. Second, RNA interference was discovered, an innate cellular pathway to control gene expression within cells. These discoveries afforded scientists the information necessary to move forward with controlling gene and protein expression profiles. More recently, CRISPR-cas technology was discovered, which allows scientists to permanently edit the genetic code by either regulating genes or adding, disrupting, deleting, or altering the specific base-pairs within the DNA sequence. Herein, we investigate several classes of polymers and macromolecules for the complexation and delivery of nucleic acid, including: amino acids, dendrimers, micelles, and linear homo- and block polymers. Initially, it was shown that polymer type, length, charge, dispersity, and composition greatly affect the efficacy of these therapeutic delivery vehicles. With this in consideration we set out to explore some of the fundamental properties of polymeric vectors. Diblocks, triblocks, and statistical copolymers were designed and synthesized with varying amounts of primary and tertiary amines. These were complexed with pDNA to from polyplexes and probed for their toxicity, stability, gene expression profiles, and mechanisms of membrane permeability. Amphiphilic polymers were also synthesized, which in aqueous environments spontaneously self assembled into core-shell structured micelles. These were probed for their ability to change size in different buffers and form different sized aggregates with DNA.Item Supporting data for Preparation and characterization of H-shaped polylactide(2024-05-16) Zografos, Aristotelis; Maines, Erin, M; Hassler, Joseph, F; Bates, Frank, S; Hillmyer, Marc, A; hillmyer@umn.edu; Hillmyer, Marc, A; University of Minnesota Department of ChemistryThese files contain primary data along with associated output from instrumentation supporting all results reported in Zografos et al. Preparation and Characterization of H-Shaped Polylactide. In Zografos et al. we developed an efficient strategy for synthesizing H-polymers. An H-polymer has an architecture that consists of four branches symmetrically attached to the ends of a polymer backbone, similar in shape to the letter ‘H’. Here, a renewable H-polymer efficiently synthesized using only ring-opening transesterification is demonstrated for the first time. The strategy relies on a tetrafunctional poly(±-lactide) macroinitiator, from which four poly(±-lactide) branches are grown simultaneously. Proton nuclear magnetic resonance (1H-NMR) spectroscopy, size exclusion chromatography (SEC), and matrix assisted laser desorption/ionization (MALDI) spectrometry were used to verify the macroinitiator purity. Branch growth was probed using 1H-NMR spectroscopy and SEC to reveal unique transesterification phenomena that can be controlled to yield architecturally pure or more complex materials. H-shaped PLA was prepared at the grams scale with a weight average molar mass Mw > 100 kg/mol and narrow dispersity Ð < 1.15. Purification involved routine precipitations steps, which yielded products that were architecturally relatively pure (~93%). Small-amplitude oscillatory shear and extensional rheology measurements were used to demonstrate the unique viscoelastic behavior associated with the H-shaped architecture.