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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.
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Fabrication Of Poly (dl-lactic-co-glycolic Acid) Nanoparticles And Synthetic Peptide Drug Conjugate For Anti-cancer Drug DeliverySen, Gulseren Petek 01 January 2010 (has links) (PDF)
Cancer is a group of diseases in which normal cells are converted to cells capable of autonomous growth and invasion. In the chemotherapeutic control of cancer, drugs are usually given systemically so they reach toxic levels in healthy cells as well as cancer cells. This causes serious side effects. Another important problem with chemotherapy is resistance developed to cytotoxic drugs (multi drug resistance).
Doxorubicin (Dox) occupies a central position in the treatment of breast cancer. However doxorubicin induced cardiac toxicity is associated with a high incidence of morbidity and mortality. Resistance of malignant tumors to Dox is another important cause of treatment failure in patients with cancer.
One approach to overcome Dox-related toxicity is to use polymeric drug carriers, which direct the Dox away from heart tissue, and allow usage of lower dosages. In this present study two different anti-cancer drug delivery methods were evaluated. Dox was encapsulated in PLGA microparticles by single and double microemulsion solvent evaporation techniques. The highest entrapment of doxorubicin within PLGA microspheres obtained by optimization of process parameters. A sustained release of doxorubicin was obtained for 20 days.
Several protein transduction domains are known to have the ability to pass through biological membranes. One such peptide is HIV-1 TAT. In this study TAT was evaluated for its ability to carry Dox into Dox resistant MCF-7 tumor cells. Dox peptide conjugate was more potent than free drug. The concentration of drug in resistant cancer cells was increased indicating a partial reversal of drug resistance.
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Lipossomas funcionalizados com peptídeos de transdução de membrana para administração intranasal de insulina no tratamento do diabetes mellitus /Von Zuben, Eliete de Souza January 2019 (has links)
Orientador: Marlus Chorilli / Resumo: O diabetes mellitus (DM) é uma síndrome metabólica caracterizada por deficiência na produção/secreção pancreática de insulina e/ou resistência à ação do hormônio nos tecidos alvo, resultando em hiperglicemia. Diversas pesquisas têm desencadeado o desenvolvimento de novos sistemas de administração de insulina que possibilitem a utilização de vias alternativas à parenteral, com destaque à administração de insulina por via nasal. Esta via tem-se mostrado promissora, pois pode promover uma rápida absorção do fármaco e aumentar a sua biodisponibilidade. Entretanto, existem mecanismos de depuração mucociliar que limitam a administração de fármacos, além da baixa permeabilidade do epitélio nasal, o qual dificulta a absorção de fármacos com alto massa molar. Uma estratégia para vencer tais barreiras é a utilização de sistemas nanoestruturados (lipossomas), pois são amplamente utilizados para o aperfeiçoamento da potencialização da ação terapêutica de fármacos. Além disso estes lipossomas foram funcionalizados com peptídeos de transdução de membrana (CPPs), tais como os peptídeos TAT e Penetratin (PNT), que atuam como promotores da penetração e absorção do fármaco, com posterior dispersão em hidrogel de hidroxietilcelulose. O objetivo deste trabalho foi desenvolver e caracterizar lipossomas contendo solução de insulina, funcionalizados com CPPs (TAT e PNT) e dispersos em hidrogel, avaliar o potencial pela via nasal, in vivo, para a melhora dos níveis séricos e efeito hipoglicemiante d... (Resumo completo, clicar acesso eletrônico abaixo) / Doutor
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Cell-penetrating peptide-enhanced delivery of heat shock proteins in models of neurodegeneration / Transport von Hitzeschockproteinen durch Zell-penetrierende Peptide in Modellen der NeurodegenerationNagel Florian 30 April 2008 (has links)
No description available.
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Expression of human α-N-Acetylglucosaminidase in Sf9 insect cells: effect of cryptic splice site removal and native secretion-signaling peptide addition.Jantzen, Roni Rebecca 15 August 2011 (has links)
Human α-N-Acetylglucosaminidase (Naglu) is a lysosomal acid hydrolase
implicated in tthe rare metabolic storage disorder known as mucopolysaccharidosis type
IIIB (MPS IIIB; also Sanfilippo syndrome B). Absence of this enzyme results in
cytotoxic accumulation of heparan sulphate in the central nervous system, causing mental
retardation and a shortened lifespan. Enzyme replacement therapy is not currently
effective to treat neurological symptoms due to the inability of exogenous Naglu to
access the brain. This laboratory uses a Spodoptera frugiperda (Sf9) insect cell system to
express Naglu fused to a synthetic protein transduction domain with the intent to
facilitate delivery of Naglu across the blood-brain barrier.
The project described herein may be broken down into three main sections.
Firstly, the impact of two cryptic splice sites on Naglu expression levels was analyzed in
both transiently expressing Sf9 cultures and stably selected cell lines. Secondly, the
effectiveness of the native Naglu secretion-signaling peptide in the Sf9 system was
examined. Finally, purification of a Naglu fusion protein from suspension culture
medium was performed using hydrophobic interaction chromatographic techniques.
The ultimate goal of this research is to develop an efficient system for
economical, large-scale production of a human recombinant Naglu fusion protein that has
the potential to be successfully used for enzyme replacement therapy to treat MPS IIIB. / Graduate
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