Doctor of Philosophy (PhD)
Liposomes have had a long and fruitful application of drug delivery devices in the treatment of select tumors and cancer types. Third-generation liposomes possess endogenous triggering methods that hold the ability for site-specific unloading of liposomal contents, thus providing necessary temporal and spatial control over contents release that can be tuned to match the drug efficacy for decreased side effects during treatment. Of these new endogenous triggers, redox-active liposomes that can be triggered to unload contents via two-electron reduction by enzymes or chemical means have demonstrated promise for the encapsulation and delivery of cargo. The research project undertaken involved the study in the mechanisms responsible for the unloading of contents from redox-active, trimethyl-locked, quinone-capped DOPE (Q3-DOPE) liposomes. It is envisioned that the local environment surrounding the liposomes is responsible for the phase behavior and rate of contents unloading due to the influence of the phase conversion of DOPE. Once the capping quinone headgroup is removed via lactone formation, lamellar phase DOPE liposomes are expected to come into close approach, aggregate, and release their contents by phase conversion to nonlamellar inverted hexagonal phase DOPE. To that end, the research here involved measurement of the rate of phase conversion through (1) study of the experimental temperature differences on the phase conversion temperature to drive contents unloading and (2) the effects of Hofmeister anion salts on the rate of contents unloading. Study of both of these lead to the hypothesis that the interfacial water layer is critical in the close approach and aggregation rate of lamellar DOPE liposomes and the presence of the Hofmeister anions assists in regulation of the water layer.
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Forsythe, Jerimiah, "Kinetics and Mechanisms of Release by Redox-Active Liposomes in Drug Delivery" (2011). LSU Doctoral Dissertations. 3252.
McCarley, Robin L.