BME PhD Prospectus Defense – Emily Lough

11:00 am on Tuesday, July 29, 2014
44 Cummington Mall, Room 401
Title: "Co-delivery of Cisplatin and Paclitaxel in
Targeted Lipid-Polymer Hybrid Nanoparticle"

Tyrone Porter, PhD (Research Advisor, Chair)
Mark Grinstaff, PhD
Allison Dennis, PhD
Jianlin Gong, MD

As the most deadly gynecological malignancy in the developed world, ovarian cancer is receiving insufficient attention in contemporary cancer research. It is a pervasive disease that’s typically detected too late to successfully treat and cure due to a deficiency of accurate screening tests. Several drugs exist that are effective in eradicating ovarian cancer cells, but the method of administration of the drug leads to limited efficacy. By administering chemotherapeutics intravenously, the clinician must strive to attain a balance between cytotoxicity of cancer cells and off-target toxicities that can be seriously debilitating to the patient. To solve this problem, this project aims to package two of the most potent chemotherapeutic agents in treating ovarian cancer: cisplatin and paclitaxel. Dual encapsulation and delivery is achieved with the development of a novel lipid-polymer hybrid nanoparticle. First, cisplatin is conjugated to a biodegradable polymer in order to increase the drug solubility in organic solvents. Nanoparticles co-loaded with paclitaxel can then be formed using a nanoprecipitation method, and coating the nanoparticles with phospholipids produces a drug delivery platform that is biocompatible, long-circulating, and can deliver multiple drugs to the same cells. By targeting the folate receptor endocytic pathway, the hybrid nanoparticle can deliver cisplatin and paclitaxel specifically to ovarian cancer cells, thus enhancing the potency of the drugs while avoiding the off-target toxicities associated with conventional systemic administration. Ultimately, the proposed hybrid nanoparticle could transform the manner in which chemotherapy is administered to patients diagnosed with advanced ovarian cancer.