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Involvement of Lipids in the Physicochemical and in vitro Characteristics of Polymer-Lipid Nanoparticles in Cancer Cell Models

Liu, Fuh-Ching Franky. University of Toronto (Canada). ProQuest Dissertations Publishing, 2019. 13427751.

Abstract (summary)

Polymer-lipid nanoparticles (PLN) have been a focus in cancer chemotherapy research due to their potential for targeting tumour cells, overcoming drug resistance and reducing toxicity. This work explores the (1) impact of “lipid” component properties and formulation parameters on PLN physicochemical properties and in vitro cytotoxicity using statistical design-of-experiments, and (2) mechanisms of PLN cell entry and organelle distribution, and response to lysosomal environments. These analyses show effects of melting point and chemical structure of multiple fatty acids/esters, and long heat exposure on PLN properties. As a result, a robust PLN system was optimized as a doxorubicin (DOX) delivery system for human glioblastoma U87-MG-RED-FLuc cells. This PLN system demonstrated intracellular internalization by multiple cell mechanisms. Furthermore, mechanistic studies examined the role of not only the optimized PLN in glioblastoma cells, but also in a previously-studied myristic acid-based PLN in breast tumour cells on improved potency over free drug.

Indexing (details)


Title
Involvement of Lipids in the Physicochemical and in vitro Characteristics of Polymer-Lipid Nanoparticles in Cancer Cell Models
Author
Liu, Fuh-Ching Franky
Publication title
ProQuest Dissertations and Theses
Publication date
2019
Pages
151
Source type
Dissertations & Theses
Language of publication
English
Document type
Dissertation/Thesis
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.