Browsing by Subject "Polymers in medicine"

Now showing 1 - 5 of 5

Biodegradable electroactive materials for tissue engineering applications
(2008-12) Guimard, Nathalie Kathryn, 1979-; Schmidt, Christine E.; Sessler, Jonathan L.
This dissertation focuses on the development of biomaterials that could be used to enhance the regeneration of severed peripheral nerves. These materials were designed to be electroactive, biodegradable, and biocompatible. To render the materials electroactive the author chose to incorporate conducting polymer (CP) units into the materials. Because CPs are inherently non-degradable, the key challenge was to create a CP-based material that was also biodegradable. Two strategies were explored to generate a biodegradable CP-based material. The first strategy centered around the incorporation of both electroactive and biodegradable subunits into a copolymer system. In the context of this approach, two bis(methoxyquaterthiophene)-co-adipic acid polyester (QAPE) analogues were successfully synthesized, one through polycondensation (giving undoped QAPE) and the second through oxidative polymerization (giving doped QAPE-2). QAPE was found to be electroactive by cyclic voltammetry, bioerodible, and cytocompatible with Schwann cells. QAPE was doped with ferric perchlorate, although only a low doping percentage was realized (~8%). Oxidative polymerization of a bis(bithiophene) adipate permitted the direct synthesis of doped QAPE-2, which was found to have a higher doping level (~24%). The second strategy pursued with the goal of generating an electroactive biodegradable material involved covalently immobilizing low molecular weight polythiophene chains onto the surface of crosslinked hyaluronic acid (HA) films. HA films are not only biodegradable and biocompatible, but they also provide mechanical integrity to bilayer systems. Dicyclocarbodiimide coupling of carboxylic acids to HA alcohol groups was used to functionalize HA films. The HA-polythiophene composite is still in the early stages of development. However, to date, thiophene has been successfully immobilized at the surface of HA films with a high degree of substitution. The author has also shown that thiophene polymerization can be achieved at the surface of these functionalized films and that the extent of polymer immobilization appears to be affected by the presence of immobilized thiophene. The results reported in this dissertation lead the author to suggest that it is possible to generate biodegradable electroactive materials. Further, she believes that with additional optimization these materials may prove beneficial for the regeneration of peripheral nerves and possibly other tissues that respond favorably to electrical stimulation.
Configurationally imprinted biomimetic polymers with specific recognition for oligopeptides
(2006-12) Lauten, Elizabeth Hunter, 1979-; Peppas, Nicholas A., 1948-; Brannon-Peppas, Lisa, 1962-
The over-expression of several peptides and proteins in the body often leads to catastrophic physiological conditions. Ultimately it would be beneficial to be able to reduce the circulation of these peptides. To achieve this, we created systems that use synthetic biomaterials to mimic natural biological recognition processes. These recognitive polymer systems can be fabricated with molecular architectures possessing specific chemical moieties that provide a framework for selective recognition of a target analyte in aqueous environments. We concentrate on a particular peptide, angiotensin II, which would benefit from a system such as this. This work reports on a novel recognitive system that recognizes and captures the undesirable analyte. To achieve destruction of the over-expressed peptide for further therapeutic effects, we have incorporated biodegradable components into the polymer backbone which create an acidic microenvironment, capable of destroying the peptide, upon hydrolytic cleavage at the ester bond. Imprinted polymer networks were prepared by UV-initiated, free radical polymerization reactions of acrylamide as the functional monomer, poly(ethylene glycol dimethacrylate) as the crosslinking agent, and angiotensin II as the template molecule. To analyze the effectiveness of the imprinting process, recognitive/binding studies using angiotensin II and its derivative SVA angiotensin were conducted by HPLC. In order to optimize the repeated recognition (rebinding) of angiotensin II, the molar ratio of template to functional monomer was varied from 1:8, 1:16 to 1:32. The cross-linking ratio was also varied from 10% to 80%. The angiotensin II was then placed in various acid compositions and analyzed by mass spectroscopy in order to determine its integrity in the presence of an acidic microenvironment. The recognition studies showed that the networks imprinted for angiotensin II were more selective and recognized angiotensin II more effectively than the non-imprinted polymers and was more selective for angiotensin II than its derivative peptide SVA angiotensin. It can also be seen from studies that the peptide angiotensin II can be degraded in the presence of glycolic acid. The synergistic effect of the recognition, capturing and destruction of the peptide ultimately offers promise for novel drug delivery systems.
Influence of drug-polymer interactions on the processing and functionality of anionic polymeric targeted drug delivery systems
(2002-12) Bruce, Lisa Diane; McGinity, James W.
Novel pH-responsive microgels and nanogels as intelligent polymer therapeutics
(2008-08) Fisher, Omar Zaire, 1979-; Peppas, Nicholas A., 1948-
Disease processes that are currently among the leading causes of death now require much more than just a stethoscope for diagnosis and a pill for treatment. The next generation of therapeutics needs to possess a degree of intelligence; the ability to sense and respond to their environment. Biomedical hydrogels have the ability to sense and respond to external stimulus and with the advent of nanotechnology; these polymers can be fabricated on the same size scale as cellular and sub-cellular processes. Throughout the body gradients in pH are used at the cellular level to regulate processes such nutrient transport and to fight infection. Sites of damage or disease within the body are associated with both a change in pH and abnormal nanoporous vasculature. pH-Responsive microgels and nanogels are small enough to access these locations within the body, sense the change in environment, and locally release a therapeutic agent In this work heterogeneous, photoinitiated free radical polymerizations were developed to synthesize novel pH-responsive microgels and nanogels that could be loaded with macromolecular therapeutics and could respond to either a basic or acidic change in pH. A novel photo-dispersion polymerization scheme was developed to synthesize poly(ethylene glycol) grafted poly(methacrylic acid) (P(MAA-g-PEG)) polycomplexation gels for oral protein delivery. These ranged in size from 100- 300 nm in diameter and could swell up to a 17-fold increase in volume, in response to a rise in pH. This property allowed them to protect insulin at low pH and release the protein at neutral pH. In this way the carriers could be used to transport proteins through the stomach to the small intestine for absorption. A novel photo-emulsion polymerization scheme was developed to synthesize poly(ethylene glycol) grafted poly[2-(diethylamino)ethyl methacrylate] nanogels, between 70-150 nm in diameter. These could swell up to a 22-fold increase in volume, in response to a drop in pH. These nanostructures were able to successfully target clathrin-dependent endocytosis and deliver macromolecules to the cytosol.
Oral delivery of protein-transporter bioconjugates using intelligent complexation hydrogels
(2008-12) Shofner, Justin Patrick, 1983-; Peppas, Nicholas A., 1948-; Brodbelt, Jennifer S.
Several polymer systems including P(MAA-g-EG) and P(MAA-co-NVP) with crosslinking agents TEGDMA and PEGDMA1000, monomer-to-solvent ratios of 67:33, 60:40, and 50:50, and particle sizes of <75 microns, 90-150 microns, and 150-212 microns were synthesized for use with protein-transporter conjugates. All synthesized systems were characterized by SEM which demonstrated the visual size, surface features, and surface textures of the polymer microparticles. Insulin-transferrin and calcitonin-transferrin conjugates were successfully synthesized using the protein crosslinker SPDP, binding the two proteins with a disulfide bond. The multi-step conjugation reactions used to create the conjugates were analyzed by the use of UV spectroscopy and HPLC to ensure the quality of the final products. In both conjugation reactions, the final product yield was found to be over 70%. The in vitro loading and release characteristics for insulin-transferrin and calcitonin-transferrin were separately investigated. By testing loading and release using a number of different polymer systems with different synthesis parameters, it was possible to optimize the hydrogel carriers for use with each of the conjugates independently. Upon optimization, the ideal system for use with insulin-transferrin and calcitonin-transferrin was found to be P(MAA-g-EG) microparticles of <75 microns formed using a PEGDMA1000 crosslinker and a 50:50 monomer-to-solvent ratio for both conjugates through separate optimization processes. This optimized polymer carrier was found to release upwards of 50% of loaded insulin-transferrin conjugate and near 90% of loaded calcitonin-transferrin conjugate. The insulin-transferrin conjugate was further evaluated through the use of cellular and animal models. Using cellular models, the insulin-transferrin conjugate was shown to increase transport relative to insulin by a factor of 7, achieving an apparent permeability of 37 x 10⁹ cm/s. Also, in the presence of polymer microparticles, the insulin-transferrin conjugate increased transport by a factor of 14 times relative to insulin, achieve an apparent permeability of 72.8 x 10⁹ cm/s. The presence of the microparticles near the cells was found to improve conjugate transport by nearly 100%. The preliminary animal studies verified the successful synthesis of the insulin-transferrin conjugate as well as demonstrated the bioactivity of the insulin portion of the molecule by achieving a drop in blood glucose level upon subcutaneous injection.