Abstract
dc:description.abstract<p>Development of liposome formulation of an amphiphilic anticancer peptide using the ANTS/DPX leakage assay. The effects of lipid composition on the liposomes' resistance to an amphiphilic cyclic peptide c[KS.S.S.KWL W] were studied by the ANTS/DPX leakage assay. One or more unsaturated acyl chains in the phospholipids, small phospholipid headgroup size, the presence of cholesterol, and the presence of PEG-lipid were demonstrated as critical parameters to stabilize the liposome membrane. A liposome formulation of the peptide comprising POPE/POPC/cholesterol/C16 mPEG 2000 ceramide (20.8:31.2:40:8, mol%) was thereby developed with a peptide-encapsulation efficiency of 47.8%. The liposomal cyclic peptide exhibited dose-dependent toxicity to MCF7 human breast cancer cells and stability under incubation.</p> <p>Design, construction and in vitro characterization of a hydrazone-based convertible liposomal system for anticancer drug delivery. A novel PEG-lipid, PEG<sub>2ooo</sub>-Hz-DHG, with an acid-labile hydrazone linker between the PEG<sub>2ooo</sub> head group and the lipidic DHG moiety was synthesized. PEG<sub>2000</sub>-Hz-DHG was relatively stable at normal physiological pH 7.4, but hydrolyzed more quickly at tumor interstitium pH 6.5-7.0 and endosomal/lysosomal pH 5.0. A novel pH-sensitive "Convertible Liposome System" (CLS) was constructed comprising PEG<sub>2ooo</sub>-Hz-DHG, positively charged lipid DOTAP, and the zwitterionic phospholipid POPC (8:15:77, mol%). CLS converted from neutrally charged "stealth" liposome to positively charged liposome at tumor interstitual pH owing to the hydrolysis ofPEG<sub>2ooo</sub>-Hz-DHG. The doxorubicin-encapsulated CLS that had been pre-incubated at pH 6.5 for 30 h exhibited more intensive binding and higher toxicity to Bl6-Fl0 murine melanoma and MDA-MB-435S human breast cancer cells than doxorubicin encapsulated in pH-insensitive stealth liposome.</p>
Degree
thesis:*- Name thesis:degree_name
- Doctor of Philosophy (Ph.D.)
- Level thesis:degree_level
- Dissertation - Pacific Access Restricted
- Discipline thesis:degree_discipline
- Pharmaceutical and Chemical Sciences
- Year dc:date.available
- 2008
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Zhang, Huizhen
- Contributors dc:contributor
-
- Xin Guo
Subjects
dc:subject × 6Rights
dc:rightsIdentifiers
dc:identifier.*- Repository record dc:identifier
- https://scholarlycommons.pacific.edu/uop_etds/711
- OAI identifier oai:identifier
- oai:scholarlycommons.pacific.edu:uop_etds-1710