Browsing by Author "Murphy, Ryan P."
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Item Chain exchange in aqueous solutions of block polymer micelles(University of Delaware, 2014) Murphy, Ryan P.Amphiphilic block polymers consist of covalently linked hydrophobic and hydrophilic polymer segments. These materials spontaneously assemble into various nanoscale structures in aqueous solution such as spherical micelles, cylindrical micelles, vesicles, and other complex morphologies. Utilizing block polymer micelles as drug delivery vehicles, aqueous nanoreactors, and other dispersant technologies demands the ability to encapsulate hydrophobic molecules within the hydrophobic micelle core, which is typically achieved through organic cosolvent processing methods. While cosolvent processing is known to affect micelle dynamics and chain exchange, processing effects in a highly selective solvent after cosolvent removal are less understood. This work investigates the stability of poly(1,2-butadiene-b-ethylene oxide) (PB-PEO) core-shell spherical micelles under various processing conditions after cosolvent removal. Processing conditions such as cosolvent addition and removal, polymer concentration, temperature, solution agitation, and interfacial contact were found to influence the stability of block polymer micelles in aqueous solutions. Complementary in situ characterization methods, including dynamic light scattering, cryogenic transmission electron microscopy, and small angle neutron scattering, were used to monitor the resulting micelle size evolution and chain exchange following dialysis into water. Despite highly unfavorable PB-water interactions, micelle size relaxation was discovered in aqueous solutions when the micelles were significantly perturbed. Notably, coupled shear and interfacial effects were found to be a key driving force for chain exchange and micelle growth, which parallels findings for other macromolecular solution assemblies such as proteins. Key findings demonstrated that micelle relaxation timescales were sensitive to the agitation method, agitation rate, temperature, molecular weight, and polymer concentration. Comprehending the interplay between various processing parameters is necessary to better control the kinetic pathways for micelle chain exchange and to further develop materials for emerging applications that hinge on the stability of macromolecular assemblies in aqueous solutions.Item The nature of anisotropic particles with short-range interactions(University of Delaware, 2017) Murphy, Ryan P.Anisotropic particles are used widely to control the thermodynamic and rheological properties of pharmaceuticals, cosmetics, food products, composite materials, and cements. In particular, rod-like particle suspensions exhibit unique equilibrium and non-equilibrium states at low particle loadings due to large excluded volumes and orientation-dependent attractions. However, the coupled effects of particle shape and interactions are not quantitatively understood with regard to dynamically arrested states, such as colloidal gels and glasses. To better quantify these effects, a tunable model system of adhesive hard rods (AHR) was developed to independently control the particle aspect ratio and the temperature-dependent, short-range attractions. AHR suspensions were composed of octadecyl-coated silica rods suspended in tetradecane, which exhibit thermoreversible dynamic arrest transitions. The dynamic moduli and particle dynamics were systematically quantified using macroscopic rheological methods and microscopic quasi-elastic light scattering methods, providing a quantitative map of the gel and glass boundaries as a function of aspect ratio (L/D=3-7), particle volume fraction (0.1-0.5), and absolute critical temperatures (Tgel=25-30 C). Small-angle neutron and X-ray scattering methods were applied to probe the arrested AHR microstructure to extract an effective interaction strength between rods on a reduced temperature scale, as defined by a dimensionless sticky parameter. ☐ AHR suspensions exhibited qualitatively similar gel and glass transition behavior, but the boundaries were quantitatively shifted in L/D, volume fraction, and T. On an absolute temperature scale, the critical gel-like boundary increased with L/D, while the critical glass volume fraction decreased significantly with L/D. However, on a reduced temperature scale, the measured gel boundary was nearly independent of L/D for conditions below the hard rod glass line. This finding suggested an extended theory of corresponding states might also apply to anisotropic particle systems with short-range attractions, as observed for similar isotropic systems. These results prompted the mapping of a fundamental AHR state diagram in terms of L/D, volume fraction, and effective stickiness to compare with various rod-like systems in literature. The results of the AHR experiments showed good agreement with mode-coupling theories for adhesive rods, which closely followed the predicted hard rod glass boundaries. The proposed state diagram links the behavior of hard spheres, adhesive hard spheres, hard rods, and adhesive hard rods, providing a way to map the intersecting boundaries between states that compete for fluidity, connectivity, rigidity, phase separation, and liquid crystal formation. The tunable AHR system and dimensionless state diagram developed in this work can be used to define, guide, and predict the non-equilibrium state boundaries for other rigid molecules, polymers, anisotropic colloids, and proteins.Item PEG−Polypeptide Block Copolymers as pH-Responsive Endosome- Solubilizing Drug Nanocarriers(American Chemical Society, 2014-05-12) Quadir, Mohiuddin A.; Morton, Stephen W.; Deng, Zhou J.; Shopsowitz, Kevin E.; Murphy, Ryan P.; Epps, Thomas H. III; Hammond, Paula T.; Mohiuddin A. Quadir, Stephen W. Morton, Zhou J. Deng, Kevin E. Shopsowitz, Ryan P. Murphy, Thomas H. Epps, III, and Paula T. Hammond; Murphy, Ryan P.; Epps, Thomas H. IIIHerein we report the potential of click chemistry-modified polypeptide-based block copolymers for the facile fabrication of pH-sensitive nanoscale drug delivery systems. PEG−polypeptide copolymers with pendant amine chains were synthesized by combining N-carboxyanhydridebased ring-opening polymerization with post-functionalization using azide−alkyne cycloaddition. The synthesized block copolymers contain a polypeptide block with amine-functional side groups and were found to self-assemble into stable polymersomes and disassemble in a pH-responsive manner under a range of biologically relevant conditions. The selfassembly of these block copolymers yields nanometer-scale vesicular structures that are able to encapsulate hydrophilic cytotoxic agents like doxorubicin at physiological pH but that fall apart spontaneously at endosomal pH levels after cellular uptake. When drug-encapsulated copolymer assemblies were delivered systemically, significant levels of tumor accumulation were achieved, with efficacy against the triple-negative breast cancer cell line, MDA-MB-468, and suppression of tumor growth in an in vivo mouse model.Item Unlocking Chain Exchange in Highly Amphiphilic Block Polymer Micellar Systems: Influence of Agitation(American Chemical Society, 2014-10-14) Murphy, Ryan P.; Kelley, Elizabeth G.; Rogers, Simon A.; Sullivan, Millicent O.; Epps, Thomas H. III; Ryan P. Murphy, Elizabeth G. Kelley, Simon A. Rogers, Millicent O. Sullivan, and Thomas H. Epps, III; Murphy, Ryan P.; Kelley, Elizabeth G.; Rogers, Simon A.; Sullivan, Millicent O.; Epps, Thomas H. IIIChain exchange between block polymer micelles in highly selective solvents, such as water, is well-known to be arrested under quiescent conditions, yet this work demonstrates that simple agitation methods can induce rapid chain exchange in these solvents. Aqueous solutions containing either pure poly(butadiene-b-ethylene oxide) or pure poly(butadiene-b-ethylene oxide-d4) micelles were combined and then subjected to agitation by vortex mixing, concentric cylinder Couette flow, or nitrogen gas sparging. Subsequently, the extent of chain exchange between micelles was quantified using small angle neutron scattering. Rapid vortex mixing induced chain exchange within minutes, as evidenced by a monotonic decrease in scattered intensity, whereas Couette flow and sparging did not lead to measurable chain exchange over the examined time scale of hours. The linear kinetics with respect to agitation time suggested a surface-limited exchange process at the air–water interface. These findings demonstrate the strong influence of processing conditions on block polymer solution assemblies.