| Description |
Title: “Ultra-High Loaded Mucoadhesive Polymeric Nanoparticles for Local Treatment of Esophageal Cancer”
Committee:
Mark W. Grinstaff, PhD – BME (Advisor, Chair)
Bela Suki, PhD – BME
Tyrone Porter, PhD – ME
Yolonda Colson, MD/PhD – MGH Thoracic Surgery
Abstract:
The proposed research addresses the need for a new drug delivery system for chemotherapeutics to treat esophageal cancer. Current clinical strategies are limited by insoluble drugs, minimal drug accumulation in the tumor, and off-site toxicities. This proposal addresses these limitations by developing and evaluating an ultra-high loaded mucoadhesive polymeric nanoparticles (AmPAS-PGC-PTX NPs) comprised of a block co-polymer of an amine-functionalized poly-amido-saccharide (AmPAS) and poly(glycerol carbonate)-paclitaxel (PGC-PTX). These nanoparticles have unique and specific properties to increase the residence time of paclitaxel around the tumor, as the AmPAS will adhere to the mucosal membrane of the esophagus and the PGC-PTX provides high drug loading for increased PTX delivery to the tumor. The increased residence time and local delivery will also decrease off-site effects. In Aim 1, the fellow will synthesize a library of block co-polymers and polymeric nanoparticles. In Aim 2, the fellow will measure PTX release and utilize both cell culture and microscopy technique to evaluate the pharmacokinetics, cytotoxicity, and mucoadhesivity of the AmPAS-PGC-PTX NPs. Understanding these characteristics will be crucial for Aim 3, where the fellow will evaluate the NPs efficacy in an in vivo orthotopic esophageal cancer model by monitoring tumor size, burden, nanoparticle biodistribution, and tissue/blood drug concentration.
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