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| Identifier |
000299708 |
| Title |
Διερεύνηση της σταθερότητας λιπιδικών μικροσφαιριδίων ως φορέων ανοσολογικών παραγόντων |
| Alternative Title |
Investication of the stability of lipid microsphares as immune_carriers |
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Author
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Τσικαλάς, Ιωάννης Γ
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Thesis advisor
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Ρίζος, Απόστολος
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| Abstract |
Certain amphiphilic water-soluble polymers including amphiphilic derivatives of poly-N-vinylpyrrolidone (PVP) were found to be efficient steric protectors for liposomes in vivo. In this study, we have tried to develop synthetic pathways for amphiphilic PVP and investigate the influence of the hydrophilic/hydrophobic blocks on the properties of resulting polymers and polymer-coated liposomes. ESR-spectra with the Doxyl spin-probe, in the presence of amphiphilic PVP demonstrated good accessibility of terminal stearyl-groups for the interaction with other hydrophobic ligands. Stearyl-PVP forms stable micelles and it was found that amphiphilic PVP with Mw between 1500 and 8000 provides good steric protection for liposomes. We have investigated on the basis of different amphiphilic water-soluble derivatives of PVP the properties of new nanoscaled polymeric carriers. The polymer self-assembly and interaction with model proteins (Bowman–Birk soybean proteinase inhibitor (BBI) and its hydrophobized derivatives) were studied in aqueous media. The possibility of inclusion of both BBI and hydrophobized oleic acid derivatives of BBI in amphiphilic PVP aggregates was explored. We have also investigated biophysical parameters of liposome constructs with embedded lipopeptides from the principle neutralizing domain of the V3-loop of the HIV-1 gp120 and their influence on viral infectivity. The V3-loop alters host cell immune function and modulates infectivity. Dynamic light scattering measurements showed liposome supramolecular structures with hydrodynamic radius of the order of 900 and 1300 nm for plain and V3-lipopeptide liposomes. Electron paramagnetic resonance measurements showed almost identical local microenvironment. The difference in liposome hydrodynamic radius was attributed to the fluctuating ionic environment of the V3-lipopeptide liposomes. In vitro HIV-1 infectivity assays showed that plain liposomes reduced virus production in all cell cultures, probably due to the hydrophobic nature of the aggregates. Liposomes carrying V3-lipopeptides with different cationic potentials restored and even enhanced infectivity. These results highlight the need for elucidation of the involvement of lipid bilayers as dynamic components in supramolecular structures and in HIV-1 fusion mechanisms.
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| Language |
Greek |
| Subject |
Amphiphilic polymers ofpvp |
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Dynamic light scattering (dls) |
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Electron paramagnetic resonance (epr) |
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HIV infectivity |
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Liposomes |
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Nanopeptides |
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V3-lipopeptides |
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V3-λιποπεπτίδια |
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Αμφιφιλικά πολυμερή της πολυβινυλοπυρρολιδόνης |
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Δυναμική σκέδαση φωτός |
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Ηλεκτρονικός παραμαγνητικός συντονισμός |
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Λιποσωμάτια |
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Μολυσματικότητα ιού AIDS |
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Νανοσωματίδια |
| Issue date |
2007-05-16 |
| Collection
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School/Department--School of Sciences and Engineering--Department of Chemistry--Doctoral theses
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Type of Work--Doctoral theses
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| Notes |
Βιβλιογραφία : σ. 153-162. |
| Views |
251 |
Διερεύνηση της σταθερότητας λιπιδικών μικροσφαιριδίων ως φορέων ανοσολογικών παραγόντων
