Toxic effects have been reported for positively-charged liposomes containing stearylamine (SA-liposomes). We have observed that hemolysis and turbidity changes in native plasma were induced by the presence of SA-liposomes. In order to study the mechanism of the SA-liposomes toxicity to blood, we have examined the interaction of SA-liposomes with erythrocyte ghosts (EG) by resonance energy transfer for the lipid mixing and by Terbium/Dipicolinate (Tb/DPA) assay for the mixing of aqueous contents. The results demonstrate that SA-liposomes and EG, after aggregation, have a tendency to mix their lipid before mixing of their internal contents. This interaction was reduced by the presence of 10$ sp{-3}$ or 10$ sp{-2}$% (w/v) carboxymethyl chitin (CMC). / We have also explored the properties of the association of SA-liposomes with CMC, using fluorescein labeled CMC (Flu-CMC). The polarization value of Flu-CMC increased upon SA-liposomes binding, the amount of Flu-CMC on the liposome surfaces increased with increase in the concentration of phospholipid and SA, and it decreased by 20-40% in the presence of 10 mM Ca$ sp{2+}.$ These results indicate that association of SA-liposomes to CMC reduces the propensity of SA-liposomes to interact with blood components and this association is due to predominantly electrostatic interactions and possibly some hydrophobic interactions between SA-liposomes and CMC. / Finally, using the resonance energy transfer assay, preliminary results indicate that there is lipid mixing between SA-liposomes and platelets. This is not inhibited by phagocytosis inhibitors such as EDTA, 2,4-dinitrophenol with iodoacetate and cytochalasin B, suggesting that the lipid mixing is not accompanied by phagocytosis of SA-liposomes by platelets.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.22751 |
| Date | January 1994 |
| Creators | Lam, Robert Tai-Thinh |
| Contributors | Nishiya, Takako (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001440696, proquestno: MM05574, Theses scanned by UMI/ProQuest. |
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