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Nanotechnology for efficient delivery of short therapeutic oligonucleotides (antisense ODN and siRNA) and codelivery with chemical anticancer drugs for effective cancer therapyChen, Minhua, January 2009 (has links)
Thesis (Ph. D.)--Rutgers University, 2009. / "Graduate Program in Chemistry." Includes bibliographical references.
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Degradable poly(ethylene glycol) based hydrogels for pulmonary drug delivery and in vitro T cell differentiation applicationsFleury, Asha Tarika 08 October 2013 (has links)
Hydrogels, defined as three-dimensional, hydrophilic networks, offer extensive biomedical applications. The areas of application are heavily concentrated in drug delivery and tissue engineering because of the hydrogels’ ability to mimic extracellular matrixes of tissue while maintaining a high level of biocompatibility. Specifically, poly(ethylene glycol) (PEG) is a well-established biomaterial in hydrogel applications due to its high water-solubility, low toxicity, high biocompatibility, and stealth properties.
This thesis discusses two applications of PEG-based degradable hydrogels. The first is the targeted, site-specific, controlled release of biologic drugs administered by inhalation. There are many challenges to designing a pulmonary delivery system for inhalation of biologic drugs such as low respirable fractions and short resident time in the lungs. In this report, the hydrogel microcarriers for encapsulated drugs were formed by cross-linked PEG and peptide sequences synthesized during a mild emulsion process. The microgels underwent freeze-drying in the presence of cryoprotectants and formulated for dry powder inhalation. The microgels displayed swelling properties to avoid local macrophage clearance in the lungs and exhibited triggered release and degradation in response to enzyme for disease specific release. Dry formulations were tested for aerosolization properties and indicated ability to be delivered to the deep lung by a dry powder inhaler. Lastly, microgels were successfully delivered to mice lungs via intratracheal aerosol delivery.
This thesis also discusses the use of PEG-based hydrogel as a biomaterial microenvironment for encapsulated stem cells as a means of in vitro T cell differentiation. A 3D hydrogel system creates a biomimetic reconstruction of the cell’s natural microenvironment and allows us to adjust factors such as ligand density and mechanical properties of the hydrogel in order to promote cells differentiation. This report utilizes hydrogels of cross-linked hyaluronic acid and PEG to encapsulate mice bone marrow hematopoietic progenitor cells in the presence of notch ligands, displayed through stromal cells, magnetic microbeads, or immobilized within the hydrogel matrix. Mechanical properties of the hydrogels were tested and the release of encapsulated cells was performed by enzymatic degradation or dissolution. The differentiation data obtained indicated successful differentiation of stem cells into early T cells through the hydrogel system. / text
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Simultaneous, single-carrier delivery of antigens and immune-modulatory molecules to dendritic cellsDawson, Eileen Regina 11 August 2015 (has links)
Immunotherapy as a means for cancer treatment has been investigated for over a century. While studies have been completed using different immunological strategies, development of a clinical therapeutic cancer vaccine has proven elusive. Recently, success has been seen with prophylactic vaccines for cancers with known viral origins (Gardasil® and Cervarix for Human Papiloma Virus). However, such strategies do not address the challenge in generating effective immune response against other tumor antigens, most of which are weakly immunogenic self-antigens. Tolerance to these self-antigens could ultimately limit the patient’s ability to mount an effective anti-tumor immune response.
The US Food and Drug Administration recently approved the first DC cell-based cancer vaccine, Provenge®, for use in prostate cancer. This vaccine requires cell isolations from the patient as well as in vitro DC modifications, which ultimately leads to high cost as well as multiple procedures. However, results indicate that, on average, patients live only four months longer than those receiving a placebo. While this work remains important, and offers proof that priming DCs can improve the lifespan of a patient, it ultimately does not offer a long-term cure. Direct and highly efficient in vivo delivery of antigens to DCs could overcome the challenges associated with ex vivo DC manipulation and may offer a more scalable method for generating anti-tumor immunity.
This research focuses on the development of novel formulations that allow simultaneous delivery of protein/peptide-based tumor antigens and immune-modulatory nucleic acids (siRNA and immune stimulatory CpG) to the same dendritic cells (DCs) in-vivo. Such formulations allow a synthetic immune-priming center to be created at the site of immunization and simultaneously deliver the tumor antigen to DCs and modulate their immune response through IL-10 silencing. Our hypothesis is that using such a DC-targeted dual delivery system we will be able to illicit strong T helper 1 (TH1) and Cytotxic T Lymphocyte (CTL) response in vivo against a wide array of tumor antigens. This can become a platform technology where the biomolecules (antigen and immunomodulatory agents) can be easily varied based on particular cancers. / text
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Design, synthesis, and evaluation of synthetic particulate delivery systems in DNA and protein vaccine deliveryKasturi, Sudhir Pai 28 August 2008 (has links)
Not available / text
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Physical and chemical properties of rapid-release systems prepared by a thermal granulation techniqueKoleng, John Joseph 09 June 2011 (has links)
Not available / text
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Substrate studies on PepT1Foley, David William January 2008 (has links)
No description available.
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Fibrin gel as a delivery system for drugs, therapeutic proteins, and cellsHyatt, Alexander James Thompson January 2011 (has links)
No description available.
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Self-assembled Polymeric Nanoparticles for Targeted Delivery of Anticancer DrugsShi, Meng 26 February 2009 (has links)
Targeted delivery of drugs to specific regions of the body, or even to specific regions of the cell, promises enhanced drug efficacy and reduced systemic toxicity. By covalently coupling targeting ligands, the smart drug delivery systems are capable of targeting specific cell types exclusively through ligand-receptor interactions. The main goal of the project is to create a polymeric nanoparticle drug delivery system from synthesized biodegradable polymers and modify the polymeric nanoparticles using targeting antibodies for targeted delivery of anticancer drugs.
A new biodegradable copolymer poly(2-methyl, 2-carboxy trimethylene carbonate-co-D,L-lactide)-graft-poly(ethylene glycol)-furan (poly(TMCC-co-LA)-g-PEG-furan) was synthesized and characterized. The copolymers self-assembled into spherical nanoparticles in aqueous environments with the hydrodynamic diameters controlled over a broad size range. Immuno-polymeric nanoparticles were created by coupling maleimide-modified anti-human epidermal growth factor receptor 2 (anti-HER2) antibodies to the self-assembled nanoparticles through Diels-Alder (DA) chemistry. This new coupling methodology was demonstrated to be relatively rapid, highly efficient and specific under mild conditions. In vitro studies showed that the immuno-nanoparticles bound specifically and efficiently with SKBR3 breast cancer cells that overexpress HER2 receptors.
Anticancer drugs were incorporated into the immuno-nanoparticle system and the drug delivery via an antibody-mediated targeting mechanism was investigated in vitro. First, a protein anticancer drug, interleukin-2 (IL-2), was physically encapsulated through polymer-drug association. The IL-2 encapsulated anti-HER2 immuno-nanoparticles exhibited a cell-binding associated IL-2 release in the extracellular space upon binding with HER2-overexpressing SKBR3 breast cancer cells. Second, a small molecule hydrophobic drug, doxorubicin (DOX), was chemically conjugated on the nanoparticle surface after the antibody coupling, using the same DA chemistry. The novel formulation localized DOX in the cell nucleus of HER2-overexpressing SKBR3 breast cancer cells and remained the biological function of conjugated DOX. Compared to the nanoparticles bearing DOX or anti-HER2 antibody alone, the nanoparticles having a combination of DOX and anti-HER2 antibody exhibited the most significant cytotoxicity and specificity against SKBR3 cells relative to healthy HMEC-1 endothelial cells, demonstrating the potential of the DOX-immuno-nanoparticles as a novel platform for intracellular DOX delivery.
This work provides a novel means for the delivery of combination immunotherapy/chemotherapy to more effectively treat certain malignancies.
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Self-assembled Polymeric Nanoparticles for Targeted Delivery of Anticancer DrugsShi, Meng 26 February 2009 (has links)
Targeted delivery of drugs to specific regions of the body, or even to specific regions of the cell, promises enhanced drug efficacy and reduced systemic toxicity. By covalently coupling targeting ligands, the smart drug delivery systems are capable of targeting specific cell types exclusively through ligand-receptor interactions. The main goal of the project is to create a polymeric nanoparticle drug delivery system from synthesized biodegradable polymers and modify the polymeric nanoparticles using targeting antibodies for targeted delivery of anticancer drugs.
A new biodegradable copolymer poly(2-methyl, 2-carboxy trimethylene carbonate-co-D,L-lactide)-graft-poly(ethylene glycol)-furan (poly(TMCC-co-LA)-g-PEG-furan) was synthesized and characterized. The copolymers self-assembled into spherical nanoparticles in aqueous environments with the hydrodynamic diameters controlled over a broad size range. Immuno-polymeric nanoparticles were created by coupling maleimide-modified anti-human epidermal growth factor receptor 2 (anti-HER2) antibodies to the self-assembled nanoparticles through Diels-Alder (DA) chemistry. This new coupling methodology was demonstrated to be relatively rapid, highly efficient and specific under mild conditions. In vitro studies showed that the immuno-nanoparticles bound specifically and efficiently with SKBR3 breast cancer cells that overexpress HER2 receptors.
Anticancer drugs were incorporated into the immuno-nanoparticle system and the drug delivery via an antibody-mediated targeting mechanism was investigated in vitro. First, a protein anticancer drug, interleukin-2 (IL-2), was physically encapsulated through polymer-drug association. The IL-2 encapsulated anti-HER2 immuno-nanoparticles exhibited a cell-binding associated IL-2 release in the extracellular space upon binding with HER2-overexpressing SKBR3 breast cancer cells. Second, a small molecule hydrophobic drug, doxorubicin (DOX), was chemically conjugated on the nanoparticle surface after the antibody coupling, using the same DA chemistry. The novel formulation localized DOX in the cell nucleus of HER2-overexpressing SKBR3 breast cancer cells and remained the biological function of conjugated DOX. Compared to the nanoparticles bearing DOX or anti-HER2 antibody alone, the nanoparticles having a combination of DOX and anti-HER2 antibody exhibited the most significant cytotoxicity and specificity against SKBR3 cells relative to healthy HMEC-1 endothelial cells, demonstrating the potential of the DOX-immuno-nanoparticles as a novel platform for intracellular DOX delivery.
This work provides a novel means for the delivery of combination immunotherapy/chemotherapy to more effectively treat certain malignancies.
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A Novel Drug Delivery System: Adenosine-Loaded Chitosan NanoparticlesReid, Marla 15 November 2013 (has links)
Adenosine is currently limited in its application as a treatment for various cancers since intravenous infusion has not been successful due to enzymatic degradation. Entrapment/association of adenosine into chitosan nanoparticles offers a possible solution to this problem. Chitosan nanoparticles which are formed by ionotropic gelation.
The size, zeta potential, morphology, entrapment efficiency, and in vitro drug release were investigated. In the swollen state, nanoparticle had an average size between 425 to 515 nm and a positive zeta potential, as measured by dynamic light scattering. Particle size measured by transition electron microscopy varied between 135 to 183 nm. Average entrapment efficiency in the range of 72 to 78% was achieved depending on initial adenosine loading and an average association efficiency of 84%. Release studies show that more than 98% of the adenosine remained entrapped/associated with the chitosan nanoparticles for at least 120 hours in PBS (pH 7.4).
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