Photoinitiated destabilization of sterically stabilized liposomes for enhanced drug delivery
AuthorSpratt, Paul Anthony
AdvisorO'Brien, David F.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractThe use of liposomes for the delivery of therapeutic agents to tumor sites took a major step forward with the introduction of sterically stabilized liposomes (PEG-liposomes). Several research groups reported the increased localization of PEG-liposomes at tumor sites. Once PEG-liposomes reach these sites, it can be desirable to increase the rate of release of encapsulated compound(s). The use of radiation for this purpose is attractive, because it can be delivered in a spatially and temporally selective manner. An effective strategy for the photopertubation of PEG-liposomes relies on the photoinitiated polymerization of reactive lipids in the liposomal bilayer. Previous studies indicated that the inclusion of the photoreactive 1,2-bis[10-(2' ,4'-hexadienoyloxy)decanonyl]-sn-glycero-3-phosphocholine (bis-SorbPC17,17) among the lipids of PEG-liposomes had little effect on their permeability until the PEG-liposomes were exposed to UV light. Photoexposure increased the permeability of the PEG-liposomes 200-fold. Research in this dissertation was focused upon increasing the reactivity of PEG-liposomes to UV and ionizing radiations. Additionally, the most favorable formulations were then used for the encapsulation of chemotherapeutic compounds that are currently on the market. Results in this dissertation indicate the ability to encapsulate water soluble compounds with high efficiency and subsequently release those compounds with minimal UV light exposure and with ionizing radiation doses that approach therapeutic levels.
Degree ProgramGraduate College