Theses and Dissertations

Date of Award

7-2022

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biochemistry and Molecular Biology

First Advisor

Dr. Subhash Chauhan

Second Advisor

Dr. Bilal Bin Hafeez

Third Advisor

Dr. Murali Yallapu

Abstract

Pancreatic cancer (PanCa) is one of the leading causes of cancer-related mortalities in the U.S due to ineffective therapeutic options. Pancreatic tumors are highly desmoplastic and inhibit efficient uptake of therapeutic payloads. Paclitaxel (PTX) has been tested in PanCa therapy with marginally better clinical outcomes, but remain limited by its poor hemocompatibility, biodistribution and intracellular accumulation in tumor cells. Thus, we synthesized a next generation nanoparticle system for PTX to improve its pharmacokinetics and pharmacodynamics (PKPD) in treating PanCa. We also examined ability of the nano formulation to potentiate gemcitabine (GEM) activity in combating chemoresistance in the pancreatic tumor microenvironment (TME).We generated a multi-layered Pluronic F127 coated paclitaxel loaded poly(lactic-co-glycolic acid) nanoparticle formulation (PPNPs) which demonstrated superior therapeutic efficacy over free PTX, effectively potentiated GEM activity in the pancreatic TME, and efficiently reprogrammed oncogenic M2 macrophages to an M1 profile to maintain a pro-inflammatory phenotype.

Comments

Copyright 2022 Godwin Peasah-Darkwah. All Rights Reserved.

https://go.openathens.net/redirector/utrgv.edu?url=https://www.proquest.com/dissertations-theses/influence-paclitaxel-nanomedicine-on-pancreatic/docview/2742638915/se-2?accountid=7119

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