Graduate Thesis Or Dissertation
 

Lipid based nanocarriers for chemotherapeutic drug docetaxel and vaccine delivery

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https://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/b2773z98v

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  • Nanoscale drug delivery systems have a great impact in current medical field. These carriers have the potential to improve the efficacy and reduce the toxicity of various medicinal products. A broad variety of different lipid based carriers had been developed and used as delivery systems in the past decades. This dissertation focused on the development of solid lipid nanoparticles (SLN) as delivery systems for a chemotherapeutic agent, docetaxel, and the use of liposomes as a carrier for recombinant protein vaccines. Docetaxel is a potent anticancer drug. However, there continues to be a need for alternative docetaxel delivery systems to improve its efficacy. Docetaxel nanoparticles comprised of lecithin as the main component were engineered using two methods, the emulsion precursor method and the solvent emulsification/evaporation method. Docetaxel in nanoparticles were more effective in killing tumor cells in culture than docetaxel solution. The intravenously injected docetaxel-nanoparticles increased the accumulation of docetaxel in tumors in mice. When administered by intravenous injection or oral routes, docetaxel-nanoparticles showed antitumor activity in tumor-bearing mice. The lecithin-based nanoparticles have the potential to be a novel biocompatible and efficacious delivery system for docetaxel. Liposomes, a well-known lipid based carrier, have been investigated extensively as a vaccine delivery system. The adjuvant activities of liposomes with different net surface charges (neutral, positive, or negative) were evaluated when simply admixed with protein antigens. Immunization study in mice after subcutaneously injection of different net charged liposomes showed different antibody responses, depending on the protein antigens. Antigens (OVA, PA) admixed with the negatively charged liposomes prepared with phospholipid, DOPA, induced a strong and functional antibody response comparable to the positively charged liposomes prepared with DOTAP lipid. The negatively charged DOPA liposomes admixed with OVA also induced OVA-specific CD8⁺ cytotoxic T lymphocyte responses and significantly delayed the growth of OVA-expressing B16-OVA melanoma in a mouse model. The adjuvant activity of the negatively charged liposomes may be related to the liposome's ability (i) to upregulate the expression of molecules related to the activation and maturation of antigen-presenting cells and (ii) to slightly facilitate the uptake of the antigens by antigen-presenting cells. Simply admixing certain negatively charged liposomes with certain protein antigens of interest may represent a novel platform for vaccine development.
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