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Date of Award

2016

Publisher

North Dakota State University

Document Type

Dissertation

Degree Awarded

Doctor of Philosophy (PhD)

Program

Pharmaceutical Sciences

Department

School of Pharmacy

College

Health Professions

Faculty Advisor

Mallik, Sanku

Description

Rapid growth of cancerous cells creates a biochemically distinct microenvironment in solid tumors. Leaky vasculature, lower pH, increased levels of proteolytic enzymes, hypoxia serve as hallmarks of tumor tissues. These changes in the tumor microenvironment present with opportunities to deliver drug at the targeted tumor tissues using stimuli responsive PEGylated nanoparticles. Stimuli responsive PEGylated nanoparticles extravasate into the tumor tissues through leaky vasculature developed at the tumor site. In the tumor tissue they undergo changes in the physico-chemical properties of the nanoparticle leading to stimuli responsive release of the entrapped chemotherapeutic/imaging agents. Clinical use of PEGylated liposomal doxorubicin formulation has encouraged multiple studies to improve the efficacy of the treatment and reduce side effects of chemotherapy. Liposomes and polymersomes are nanoparticles which form a lipid or polymeric bilayer allowing entrapment of hydrophilic molecules at the core and lipophilic molecules in the bilayer. These chemically engineered drug carriers allow targeting and drug delivery preferentially at the pathologically affected tissues. Stimuli responsive liposomes and polymersomes hold tremendous potential for drug delivery to solid tumors. We have prepared tumor microenvironment responsive PEGylated liposomes and polymersomes for efficient drug delivery to pancreatic cancer cells.

Rights

NDSU Policy 190.6.2

Rights Link

https://www.ndsu.edu/fileadmin/policy/190.pdf

Handle Identifier

https://hdl.handle.net/10365/25814

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