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Improvement of longevity and signal quality in implantable neural recording systemsZargaran Yazd, Arash 05 1900 (has links)
Application of neural prostheses in today's medicine successfully helps patients to increase their activities of daily life and participate in social activities again. These implantable microsystems provide an interface to the nervous system, giving cellular resolution to physiological processes unattainable today with non-invasive methods. The latest developments in genetic engineering, nanotechnologies and materials science have paved the way for these complex systems to interface the human nervous system. The ideal system for neural signal recording would be a fully implantable device which is capable of amplifying the neural signals and transmitting them to the outside world while sustaining a long-term and accurate performance, therefore different sciences from neurosciences, biology, electrical engineering and computer science have to interact and discuss the synergies to develop a practical system which can be used in daily medicine practice.
This work investigates the main building blocks necessary to improve the quality of acquired signal from the micro-electronics and MEMS perspectives. While all of these components will be ultimately embedded in a fully implantable recording probe, each of them addresses and deals with a specific obstacle in the neural signal recording path. Specifically we present a low-voltage low-noise low-power CMOS amplifier particularly designed for neural recording applications. This is done by surveying a number of designs and evaluating each design against the requirements for a neural recording system such as power dissipation and noise, and then choosing the most suitable topology for design and implementation of a fully implantable system. In addition a surface modification method is investigated to improve the sacrificial properties and biocompatibility of probe in order to extend the implant life and enhance the signal quality.
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Curdlan 1,3-Beta-Glucans: A New Platform for Polymer Drug DeliveryLehtovaara, Benjamin 18 April 2011 (has links)
1,3-β-glucans are a class of natural polysaccharides with unique pharmacological properties and the ability to form triple helical structures and resilient gels. Curdlan and other 1,3-β-glucans have found application pharmacologically in the treatment of cancers and acceleration of wound healing in humans and in the impartation of infection resistance in animal husbandry. Structurally, these polysaccharides have found application in food science as thermal gels, in nanostructure formation as helical scaffolds, and in drug delivery as nanocarriers for drugs and as inclusion complexes with polynucleotides.
A literature review of the important work on Curdlan research reveals two streams of research: investigation of the pharmacological significance of these polymers and their application in increasing host immunocompetency and investigation of the nature of the triple helix and its application in a variety of fields from food gels to drug delivery.
Two significant contributions to the field of Curdlan research have been completed including 1) The development of a Curdlan nanoparticle drug delivery platform and 2) A new multi-component liquid crystalline hydrogel providing a new route to form polynucleotide inclusion complexes with Curdlan for gene delivery. The developed nanoparticle platform exhibited high encapsulation of chemotherapeutic drugs and a 24-hour controlled release with a particle size of 109.9 nm. The liquid crystalline hydrogel exhibited homogeneous inclusion of DNA into amorphous and crystalline phases of Curdlan and delayed and triggered release of polynucleotide content. This work has been a significant demonstration of the potential of Curdlan as a new polymer for multi-functional drug delivery.
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Design of Coated Magnetic Iron-Oxide Nanogels for Drug Delivery SystemsRahmani, Sara January 2011 (has links)
Intelligent and more advanced therapeutic agents, capable of sensing and responding to their environment, are required to treat more complicated and complex diseases. Among all recently developed therapeutic agents, hydrogels are not only intelligent to sense and respond to external stimulus, but also they can be synthesized and designed in the cellular and sub-cellular size scale, which enhance their therapeutic ability. Most body physiological processes are regulated as a consequence of pH gradient in different compartments of the body; besides, changes in pH are also associated with disease or damaged sites within the body. A unique feature of hydrogels is that they can provide a network for loading and release of drugs. Therefore, the drug loaded within pH-responsive nanogels are able to locally release onto the target sites because of their small size, and capability to sense and respond to environmental changes.
The goal of this research is to design and implement novel pH-responsive magnetic nanogels for drug delivery that respond to changes in pH. Semi-continuous emulsion polymerization was conducted to synthesize polyampholyte nanogels comprising of methacrylic acid (MAA) and 2-(diethylamino) ethyl methacrylate (DEAEMA) in the presence and absence of steric stabilizer poly (ethylene glycol) methacrylate (PEGMA). The synthesized nanogels demonstrated swelling behavior at both acidic and basic pHs. Herein, procaine hydro chloride (PrHy) was utilized as cationic drug to investigate the release behavior from synthesized nanogels under different conditions. PrHy was loaded within nanogels through hydrophobic interaction and hydrogen bonding, as confirmed by isothermal titration calorimetry. The release study of PrHy molecules from nanogels was conducted by applying the versatile and easy technique of drug selective electrode, in which the concentration of released drug was measured as a function of time.
In order to facilitate the purification and enhance the detection of nanogels, iron oxide particles (Fe3O4) were co-precipitated within nanogels to form magnetic nanogels. Subsequently, layer-by-layer coating of polyelectrolytes were performed to control and eliminate the initial burst release of PrHy from nanogel by increasing the diffusion barrier and manipulating the permeability of nanogels. For the purpose of this research low molecular weight chitosan (CS) was used as polycation and poly (sodium 4-styrenesulfonate) (PSS) was acted as polyanion to coat magnetic nanogels. The more layers was applied, the more reduction in burst release was observed, which was revealed by using drug selective electrode to measure the concentration of the released drug from coated nanogels. Besides, layer-by-layer coating prolonged the time require to reach the steady state drug release. Therefore, this synthesized polyampholyte coated iron-oxide nanogels demonstrate great potential for use in controlled drug delivery systems.
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Functionalization of Poly(Ethylene Oxide)-based Diblock Copolymer VesiclesKinnibrugh Garcia, Karym G. 2010 May 1900 (has links)
The principal goal of this research is to achieve the chemical labeling and surface modification of block copolymer vesicles (polymersomes) made from amphiphilic diblock copolymer Poly(butadiene-b-ethylene oxide) (PBd120- PEO89, MW 10400 g/mol) with the aim of developing possible drug carrier vehicles for controlled release of molecules triggered by stimuli-responsive environments.
The terminal hydroxyl group of poly(ethylene oxide) (PEO), or poly(ethylene glycol) is converted into its corresponding carboxylic acid by a novel one-pot two-phase oxidation reaction. This regioselective and catalytic reaction assures the preservation of important structural characteristic of the block copolymers. Vesicles formed by a mixture of the carboxylate and unmodified block copolymer exhibit an increment in the critical aggregation concentration (CAC) value while the averaged vesicle size decreases demonstrating that the negative charges in the modified diblock copolymer disrupt the vesicle formation process.
The carboxylated reactive intermediates are subsequently subjected to a covalent coupling reaction in organic solvent to replace the terminal hydroxyl of the PEO block. The obtained functionalized diblock copolymers are effectively incorporated into the vesicle bilayer. Also, surface density control in polymersomes of fluorescently modified diblock copolymers, synthesized by the amination reaction, is achieved.
To demonstrate the ability of this polymersomes as carrier vehicles, a Noradrenaline functionalized vesicle is placed in closed contact with rat aortic smooth muscle cells (RASMC) using the micropipette aspiration technique. A distinctive increase in fluorescent intensity of cells is observed. It indicates that the drug molecule has been transported by the polymersome and internalized by the cell. In addition, diblock copolymers containing a disulfide moiety and a fluorophore are synthesized and studied through fluorescent microscopy. Vesicles are formed with this polymer and a decrease in fluorescent intensity is observed in the vesicle's bilayer after its exposure to a reductive environment. These results indicate that fluorophore molecules are successfully released into solution.
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Microdermabrasion for transdermal drug deliveryAndrews, Samantha Nacole 27 August 2010 (has links)
The skin serves as a semi-permeable barrier that protects the body from pathogens and water loss. The stratum corneum, the upper 10-15 µm layer of skin, is the primary barrier layer. Due to its structure, only drugs that are lipophilic and with a low molecular weight (<500 Da) can penetrate intact skin. This study examines the use of microdermabrasion as a method of removing the stratum corneum to increase the skin's permeability to hydrophilic molecules, proteins, and vaccines. Microdermabrasion is a FDA-approved cosmetic skin resurfacing procedure that removes the stratum by bombarding it with abrasive particles under vacuum. The aims of this thesis are focused on optimizing the microdermabrasion conditions that will selectively remove stratum corneum, evaluating the transport of different sized molecules through abraded skin in vitro, examining drug efficacy in vivo by delivering insulin to diabetic rats, and examining the rate of skin healing after treatment. Microdermabrasion can be used as a non-invasive transdermal drug technique to safely remove stratum corneum to make the skin more permeable to waters soluble drugs and proteins.
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Synthesis and evaluation of amphiphilic scorpion-like and star macromolecules for biomedical applicationsDemirdirek, Bahar. January 2009 (has links)
Thesis (M.S.)--Rutgers University, 2009. / "Graduate Program in Chemistry and Chemical Biology." Includes bibliographical references.
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Preparation and evaluation of amphiphilic macromolecules-based conjugates and micelles for anticancer drug deliverydel Rosario, Leilani Singson. January 2009 (has links)
Thesis (Ph. D.)--Rutgers University, 2009. / "Graduate Program in Chemistry and Chemical Biology." Includes bibliographical references.
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Design of macromolecular drug delivery systems using molecular dynamics simulationPatel, Sarthakkumar Kiritkumar. January 2010 (has links)
Thesis (Ph. D.)--University of Alberta, 2010. / Title from pdf file main screen (viewed on Jan. 27, 2010). A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Chemical Engineering, [Department of] Chemical and Materials Engineering, University of Alberta. Includes bibliographical references.
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Pulmonary delivery of anorectic gut secreted peptides for appetite suppression in ratsNadkarni, Priya P., January 1900 (has links)
Thesis (Ph.D.)--Virginia Commonwealth University, 2009. / Prepared for: Dept. of Pharmaceutics. Title from title-page of electronic thesis. Bibliography: leaves 123-135.
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The utility of L-tyrosine based polycarbonate copolymers containing poly(ethylene glycol) as a degradable carrier for the release of a hydrophobic peptide moleculeKhan, Isaac John, January 2009 (has links)
Thesis (Ph. D.)--Rutgers University, 2009. / "Graduate Program in Biomedical Engineering." Includes bibliographical references (p. 183-187).
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