MSc Defence - Behnoush Kermanshahi "Development of an Oral Drug Delivery System to Improve the Bioactivity of Avocatin B"

Examining Committee

Dr. Keith Warriner, Chair 
Dr. Paul Spagnuolo, Advisor 
Dr. Michael Rogers, Advisory Committee Member  
Dr. Massimo Marcone, Department Member 

TITLE: Development of an Oral Drug Delivery System to Improve the Bioactivity of Avocatin B
 
ABSTRACT: Avocatin B, a lipid-derived from avocado, is identified as a novel anti-cancer agent capable of inducing apoptosis of leukemia and leukemic stem cells by accumulating in mitochondria. Although this avocado-derived bioactive has demonstrated anti-leukemic activity in vitro, there is concern about the bioavailability of this compound, as its poor absorption could limit its clinical use. In this study, we exploited the natural surface-active properties of avocatin B to design self-emulsifying drug delivery systems (SEDDS) that are potentially suitable for human oral consumption. In contrast to typical emulsion-based delivery systems, the formulations in this work were prepared without external energy and using only one surfactant. This provides advantages of i) a low weight ratio of emulsifying component to oil component, and ii) fewer chemical toxicity concerns. In vitro cytotoxicity testing of avocatin B-SEDDS in acute myeloid leukemia (AML) cell lines indicate significant increases in potency and bioactivity compared to conventional dimethyl sulfoxide-based delivery. A pilot pharmacokinetic evaluation of avocatin B-SEDDS in C57BL/6J mice revealed appreciable accumulation in whole blood and biodistribution in key target tissues. We anticipate that data obtained from this study will provide the necessary framework for the development of Avocado’s derivatives as therapeutic agents in the clinical setting.