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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.

The evaluation of melamine dendrimers as potential macromolecular vehicles for anticancer drug delivery

Neerman, Michael Frederick 29 August 2005 (has links)
Often associated with chemotherapy are the dangerous and sometimes lifethreatening side effects towards non-cancerous tissue that can occur while on such drug regimens. The design and utilization of macromolecular drug delivery vehicles is gaining much attention because the vascular system of tumor tissue possesses properties that make it permeable to macromolecules. The attachment or encapsulation of anticancer drugs to macromolecules can be used to selectively deliver these drugs to tumor tissue thereby minimizing the toxic effects towards healthy tissue while specifically targeting the tumor. Moreover, the association of poorly water soluble drugs with soluble macromolecules can increase the water solubility of such hydrophobic drugs. Finally, association of chemotherapeutic agents with macromolecules can also increase the drugs?? circulation time by decreasing the rate of renal clearance thus leading to improve pharmacokinetics. A class of spherical, hyperbranched polymers known as dendrimers has received much attention as potential vehicles for anticancer drug delivery. Dendrimers based on melamine might afford such use as macromolecular carriers for drug delivery. Therefore an evaluation of melamine dendrimers is reported. The goal of objective one was to assess both the in vitro and in vivo biocompatibilities of a cationic dendrimer based on melamine. The results reported herein indicate that this particular species of dendrimer is not suitable for in vivo use and did not warrant further investigation. The goals of objective two were to see what impact surface modification had on the in vitro and in vivo toxicities of a melamine dendrimer. The results presented here indicate that surface modification of a cationic dendrimer to anionic or neutral species can extensively increase biocompatibility. Moreover, the introduction of neutral poly(ethylene glycol) (PEG) grafts affords the most protection in vitro and in vivo. Interaction with albumin, controlled drug release, cellular uptake along with favorable biodistribution patterns are vital factors that must be evaluated when screening a drug delivery system. Evaluating the PEGylated dendrimer as a vehicle for anticancer drug delivery, the goal of objective three, provides initial evidence that the PEGylated dendrimer displays favorable characteristics as a vehicle for drug delivery and justifies additional studies utilizing in vivo models.

Design and mechanistic evaluation of novel pore-regulated polymer matrices for transmucosal drug delivery

Adeleke, Oluwatoyin Ayotomilola 14 February 2012 (has links)
Ph.D., Faculty of Health Sciences. University of the Witwatersrand, 2011

Polyethylene glycol (PEG) as a key component of long-circulating delivery system for therapy and imaging doctoral thesis /

Sawant, Rishikesh Manohar. January 1900 (has links)
Thesis (Ph. D.)--Northeastern University, 2008. / Title from title page (viewed Aug. 4, 2009). Graduate School, Bouvé College of Health Sciences, School of Pharmacy. Includes bibliographical references.

Synthesis and characterization of melamine-based dendrimers with potential biological applications

Crampton, Hannah Louise 15 May 2009 (has links)
The convergent strategy towards dendrimer synthesis is well-suited to generate macromolecules with a diverse periphery, at the expense of time and effort, while the divergent strategy has historically been effective at yielding higher generation dendrimers, although they are often plagued by impurities. Both the convergent and divergent routes were applied to the synthesis of melamine-based dendrimers, offering a comparison of the routes within a system. Generation-1 dendrons heterogeneously functionalized with Boc-protected amines and hydrazones were synthesized convergently and coupled to a generation-1 tris(piperazine) core to yield a generation-2 dendrimer bearing 18 Boc-amines and three hydrazones. Although the yield for the final coupling step was rather low (56%), the yields for all intermediate steps were quite high. Attempts toward obtaining a generation-3 dendrimer through this route were unsuccessful due presumably to steric hindrance. The materials obtained showed no impurities in their 1H and 13C NMR and mass spectra, although several chromatographic purifications were necessary throughout the synthesis. A divergent strategy based on addition of a dichlorotriazine monomer to polyamine cores was used to synthesize dendrimers of generations 1-5. All intermediates and dendrimers were either purified by precipitation, or did not need purification. 1H NMR spectroscopy indicated that reactions were complete up to G4-NH2 by integration, and mass spectroscopy confirmed that assignment. HPLC and GPC of Gn-Cl dendrimers showed sharp peaks for G1-G3, but G4-Cl appeared to have a small amount of impurities that are similar in size and polarity to the fully-substituted dendrimer. The G1-G3 dendrimers were confidently assigned as pure by conventional organic chemistry standards, but the assignment of purity to higher generations remained tentative. A G1-Cl dendrimer was functionalized with imidazole, and then deprotected and PEGylated with PEG5000 to yield a water soluble dendrimer. The imidazole-capped, Boc-protected dendrimer and the deprotected dendrimer were characterized by 1H and 13C NMR spectroscopy and mass spectrometry. The degree of PEGylation on the PEGylated material could not be definitively ascertained; however, the material is capable of solubilizing very hydrophobic Zn-phthalocyanines in water.

Biocompatibility Evaluation of Engineered Amino Acid Pairing Peptides for Drug Delivery

Naahidi, Sheva 27 January 2015 (has links)
To ensure the effective and safe use of nanomaterials for medical applications, the biocompatibility of the materials must be tested with particular relevance to the environment in which the material is placed. In nanoparticle-based drug delivery, it is crucial to evaluate a nanoparticle???s biocompatibility to ensure minimal cytotoxicity. Of several types of nanoparticles, peptide-based nanoparticles have emerged as promising systems for targeted cancer therapy. Yet, the biocompatibility of many of these peptides and their assembled particles has not been studied. This thesis, summarizes the original contribution on the effective and safe use of the particular self/co-assembling, amino acid pairing peptides and some of their DEGylated forms (modified versions) as carriers for anticancer drug delivery application. Therefore, the biocompatibility of the self-assembling, amino acid pairing (AAP) peptides AC8, its two DEGylated forms, as well as two related peptides, EAK16-II and EK8, is systematically investigated. The toxicity of these peptides and their complexes with pirarubicin was tested against the human adenocarcinoma lung cancer cell line, A549.The biocompatibility of the peptide-drug co-assembling complexes is assessed and the potential of these five peptides as carriers for the hydrophobic anticancer drug pirarubicin is demonstrated. For the first time experimental results on cytotoxicity, haemolytic activity, red blood cell (RBC) aggregation, complement activation and anaphylotoxin activation as an end result of complement activity for these five AAP peptides is reported. AC8, the amino end DEGylated AC8 (NP-I) and EK might be strong candidates for hydrophobic drug delivery considering their lack of toxicity and the fact that they are not recognized as a foreign molecule, inducing no considerable immune reactions. These results provide a basis for in vivo experiments and predict minimal in vitro toxicity of these peptides based delivery systems.

Analytical applications of liposomes

Frost, S. J. January 1994 (has links)
Liposomes have established roles in drug delivery and cell membrane studies. Amongst other applications; they can also be used as analytical reagents, particularly in immunoassays. Liposomal immunoassays have potential advantages over alternatives; including sensitivity, speed, simplicity and relative reagent stability. The aim of these studies was to develop and evaluate novel examples of these assays. When liposomes entrapped the dye, Sulphorhodamine B, a shift in its maximum absorption wavelength compared to free dye was observed. This was attributed to dimerization of the dye at high concentrations. If the liposomes were disrupted, the released dye was diluted into the external buffer, and the dye's absorption spectrum reverted to that of free dye. After optimization of dye entrapment, immunoassays were developed using these liposomes. Albumin-coated liposomes were used in a model assay to measure serum albumin. This assay employed complement-mediated immunolysis, commonly used in liposomal immunoassays. The liposomes were lysed by anti-albumin and complement, and this could be competitively inhibited by serum albumin. To improve sensitivity, Fab' anti-albumin liposomes were prepared. These enabled measurement of urinary albumin by a complement-mediated immunoassay, but using a sandwich technique. Anti-albumin (intact) liposomes were shown to precipitate on gentle centrifugation after reaction with albumin. They were applied as a solid phase reagent in an heterogeneous immunoassay, using radioimmunoassay for urinary microalbumin as a model assay. Liposomes containing Sulphorhodamine B were also used in a more novel assay; for serum anticardiolipin antibodies. Cardiolipin-containing liposomes were prepared. These were lysable using magnesium ions. Anticardiolipin antibodies (IgG) were found to augment this lysis, enabling their estimation. Similar imprecision and acceptable correlation with a commercial enzyme-linked immunosorbent assay (ELISA) were obtained. The findings demonstrate Sulphorhodamine B release can be used as a marker in homogeneous colorimetric liposomal immunoassays; both in model assays and in potentially more useful clinical biochemistry applications.

Metal-polymer nanoparticulate systems for externally-controlled delivery

Gran, Martin Luke 09 February 2011 (has links)
Metal-polymer nanocomposites consisting of gold nanorods and temperature-responsive hydrogel nanoparticulates were investigated for use in externally-controlled drug delivery systems. Several different thermo-responsive hydrogels including poly(N-isopropyl acrylamide) (PNIPAAm) and poly(N-isopropryl acrylamide-co-acrylic acid) (P(NIPAAm-co-AA)) nanoparticles were synthesized for these nanocomposites using an aqueous dispersion polymerization method. In addition, nanoparticles of interpenetrating polymer networks (IPN) composed of poly(acrylamide) (PAAm) and poly(acrylic acid) (PAA) were synthesized using a water-in-oil emulsion polymerization. Temperature-responsive equilibrium swelling behavior of nanoparticles with varying crosslinking densities was characterized using dynamic light scattering. IPN systems exhibited a positive swelling response upon heating while PNIPAAm and copolymer systems collapsed upon increase in temperature above the transition point. Nanoparticles were characterized using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) which demonstrated shape and morphology of polymer particles. Gold-polymer nanocomposites were formed by grafting gold nanorods to the surface of the polymer nanoparticles. Amine-functionalized gold nanorods were coupled to polymers using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and N-hydroxysulfosuccinimide (Sulfo-NHS) to activate carboxyl groups on the surface of the polymer nanoparticles. TEM confirmed successful formation of the metal-polymer nanocomposites. Loading and release of a model therapeutic were done to assess the potential use of the polymer component of the nanocomposite for drug delivery. Fluorescein, a model for chemotherapeutics, was loaded into P(NIPAAm-co-AA) polymer nanoparticulates. Loading of the compound was shown to be a function of crosslinking density in the polymer network. Maximum loading was achieved using nanoparticles synthesized with a 10 mol% crosslinker feed ratio with entrapment efficiencies of 80.0 % and loading capacities of 12.0 %. Cytotoxicity studies were performed using a NIH/3T3 mouse fibroblast cell model. Cell viabilities in presence of P(NIPAAm-co-AA) nanoparticles were comparable to (not statistically different than) controls at concentrations up to 4 mg/ml. Similarly, gold-polymer composite concentrations up to 0.5 mg/ml caused limited cell death. / text

Antibacterial agents designed to exploit peptide transport systems

Marshall, Neil J. January 1994 (has links)
No description available.

Targeted drug delivery within the eye

Kim, Yoo C. 12 January 2015 (has links)
This work introduces novel approaches to enhance targeting of pharmacotherapies to cornea, ciliary body, choroid, and posterior segment of the eye using microneedles as a drug delivery platform. The first part of the work determines the ability to deliver protein therapeutics into the cornea using coated microneedles to suppress corneal neovascularization in a rabbit model. The data show that highly targeted delivery of the anti-vascular endothelial growth factor protein therapeutic gave a better biological response of suppressing neovascularization with 11,900 times less dosage compared to topical administration. The second part of the research aims to develop novel formulations to target ciliary body and choroid via suprachoroidal delivery. The results show that a strongly non-Newtonian fluid can be used to slow down the spreading of the particles at the injection site up to 2 months. The results also show that a high molecular weight formulation with weakly non-Newtonian fluid can be used to reach 100% coverage of the choroidal surface with a single injection. The third part of the research aims to determine the biological response of targeting anti-glaucoma therapeutics to the ciliary body in a rabbit model. The results show we can achieve 500- to 1000-fold dose sparing by targeted delivery via supraciliary delivery. The fourth and last part of the research aims to develop novel emulsion droplets to target different locations within the eye using a gravity-mediated delivery technique via suprachoroidal space injection. The results show that we can deliver up to 73% of injected polymeric particles posterior to the equator of the eye. Overall this work demonstrates that microneedles have the capability to deliver pharmacotherapies to cornea, ciliary body, choroid, and posterior of the eye in a highly targeted manner and provide significant dose sparing in the rabbit model.

Physicochemical evaluation of nanoparticles assembled from block copolymers as colloidal drug carriers

Riley, Trevor January 1999 (has links)
No description available.

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