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Amphiphilic macromolecule-lipid complexes as drug delivery systems
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Harmon, Alexander M.. Amphiphilic macromolecule-lipid complexes as drug delivery systems. Retrieved from https://doi.org/doi:10.7282/T33B5ZS8

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TitleAmphiphilic macromolecule-lipid complexes as drug delivery systems
NameHarmon, Alexander M. (author); Uhrich, Kathryn (chair); Chen, K-Y (internal member); Taylor, John (internal member); Roth, Charlie (outside member); Rutgers University; Graduate School - New Brunswick
Date Created2011
Other Date2011-01 (degree)
SubjectChemistry and Chemical Biology, Drug delivery systems, Cancer--Treatment, Micelles, Paclitaxel, Liposomes
Extentxiv, 132 p. : ill.
DescriptionCancer is the second most common death in the US accounting for 25% of all deaths. Many of the potent anti-cancer drugs are insoluble in water and require drug delivery agents. However, many of these agents are therapeutically inefficient and are associated with adverse side effects. Amphiphilic Macromolecules (AM) are a novel class of micelle forming materials with drug delivery applications. A screening of amphiphilic macromolecules against primary human cells of the vasculature in vitro showed good biocompatibility. To further their drug delivery potential, AMs were physically complexed with liposomes composed of a 1:1 mix of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) for form AM-lipid complexes . Altering the AM-lipid method of assembly (co-evaporation (CE) or post-addition (PA)), as well as the AM to lipid ratios, allows the complexes to exist as either lamellar aggregates, micellar aggregates, or as AM-coated liposomes. AM-lipid complexes exhibit tunable zeta potential, steric stability, and inherently low cytotoxicity. Significantly, AM-lipid complexes exhibit a preferential uptake in carcinoma cells over normal cells in vitro demonstrating a unique, passive targeting approach to delivery anti-cancer therapeutics. AM-lipid complexes were loaded with the hydrophobic anti-cancer drug paclitaxel (PTX). The loading of PTX does not significantly affect the size of the nanocarriers. Paclitaxel-loaded 1:1 AM-lipid complexes showed drug-mediated, dose-dependent cytotoxicity towards BT-20 cell in vitro. Over thirty days, Balb/C mice systemically treated with PTX-loaded AM-lipid complexes showed higher in vivo tolerability than Taxol-treated mice. Studies investigating the thermodynamic and physical interactions between AMs and DOPE:DOTAP liposomes showed a cooperative intermolecular interactions between pure lipids and AM in monolayers and high affinity of AM micelles for DOTAP: DOPE liposomes in buffer solution respectively. Increasing the complex’s AM weight ratio in the CE method led to the complete solubilization of the vesicles from lamellar aggregates, to a mixture of co-existing vesicles and micelles, to mixed micelles. At higher AM weight ratios, PA-produced complexes exhibit greater stability than complexes at lower AM weight ratio and complexes produced by the CE methods showed stronger interactions between AM-lipid components than complexes produced by the PA method. The results suggest that the PA method produces vesicles with AM molecules associated with its outer leaflet only (i.e., an AM-coated vesicle), while the CE method produces complexes ranging from mixed vesicles to mixed micelle in which the AM-lipid components are more intimately associated. Based on these results, AM-lipid complexes show promise as a novel nanocarriers for paclitaxel delivery.
NotePh.D.
NoteIncludes bibliographical references
NoteIncludes vita
Noteby Alexander M. Harmon
Genretheses, ETD doctoral
Persistent URLhttps://doi.org/doi:10.7282/T33B5ZS8
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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