Ghazwani, Mohammed
(2016)
TARGETED DUAL FUNCTIONAL NANOPARTICLES FOR THE TREATMENT OF CANCER AND LIVER FIBROSIS.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
For decades, a large number of therapeutics have been discovered and developed with high potential for curing various diseases, many of which have been clinically used for years. However, some treatments are greatly limited due to their side effects, which arise from their inability to differentiate between normal and diseased cells. The aim of this dissertation work is to develop nanomaterial-based dual function drug delivery systems to improve overall therapeutic outcomes for the treatment of cancer and liver fibrosis.
The first part of this work focused on the development of FTS-based solid lipid nanoparticles (SLNs) for cancer-targeted delivery of paclitaxel (PTX). Novel SLNs were successfully developed which are capable of solubilizing PTX while simultaneously avoiding unwanted side effects of the clinically used PTX formulation (Taxol). The data from this study demonstrated that the PTX-SLNs system has a significantly improved profile in terms of controlled release kinetics and stability compared to Taxol. Additionally, PTX-SLNs have shown enhanced anticancer activity in vivo.
The second part focused on improved delivery of the herbal agent thymoquinone (TQ) to hepatic stellate cells (HSCs) for the treatment of liver fibrosis. Firstly, a study was conducted on the biological effects of TQ on HSCs, which represent the major liver cell type involved in the massive production of extra cellular matrix (ECM) in liver fibrosis. The results revealed that TQ exerts hepatoprotective and anti-fibrotic effects via direct inhibition of the fibrogenic activities of HSCs, which suggests that TQ holds great potential as a new drug candidate for treatment of liver fibrosis. Secondly, an examination was conducted on the potential of a novel dual functional micellar system PEG5k-Fmoc-FTS2 to deliver TQ into activated HSCs in vitro. TQ-micelles have shown high tolerability in activated HSCs with more efficient anti-fibrotic activity compared to free TQ.
Collectively, this work suggests that an FTS-based SLNs system represents a promising nanocarrier for cancer-targeted delivery which could enhance the therapeutic efficiency of anticancer agents. In addition, TQ holds a great a potential as new therapy for the treatment of liver fibrosis, and formulating TQ into the PEG5k-Fmoc-FTS2 micelles system could further enhance overall anti-fibrotic activity.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Ghazwani, Mohammed | mog7@pitt.edu | MOG7 | |
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| ETD Committee: |
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| Date: |
8 March 2016 |
| Date Type: |
Publication |
| Defense Date: |
1 December 2015 |
| Approval Date: |
8 March 2016 |
| Submission Date: |
7 March 2016 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
119 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Pharmacy > Pharmaceutical Sciences |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Solid lipid nanoparticles, Liver Fibrosis, cancer, nanomedicine, Thymoquinone, targeted delivery, Paclitaxel, Hepatic Stellate Cells, Polyethylene glycol. |
| Date Deposited: |
08 Mar 2016 19:18 |
| Last Modified: |
08 Mar 2017 06:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/27051 |
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