Xu, Jieni
(2015)
PREPARATION OF PEG-DERIVATIZED PPMP AS A DUAL-FUNCTIONAL CARRIER FOR ANTICANCER DRUGS.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Our goal is to synthesize PEG-derivatized PPMP as a dual-function carrier for anticancer drugs to co-deliver PPMP and classic anticancer drugs. The clinical application of anticancer drugs has been limited by low water solubility, rapid elimination, lack of tissue-specificity and toxicity. A number of macromolecular delivery systems are under investigation to circumvent these limitations and improve the potential of the anticancer drugs. However, for most delivery systems, vehicles themselves rarely possess pharmacological activity. One interesting approach in the design of a carrier is that components of the carrier system exhibit biological activity, either possessing antitumor effect or sensitizing tumor cells to loaded anticancer drugs. PPMP blocks glucosylation of ceramide, a tumor-suppressor lipid, which induces antiproliferative and apoptotic responses in cancer cells. We conjugate PPMP with PEG to increase solubility. At the same time, amphiphilic PEG5K-PPMP2 could self-assemble into micelles and serve as a carrier for other hydrophobic anticancer drugs. We propose that PEG5k-PPMP2 could be an effective and novel dual functional carrier for anticancer drugs.
In this thesis, the first aim was to examine the efficacy of co-treatment of PPMP with other anticancer drugs (camptothecin and doxorubicin) in different cancer cell lines. In vitro cytotoxicity studies showed more effective tumor-killing effect in the combination treatment than single drug treatment. The combination of PPMP and CPT or DOX showed synergism in all of the cancer cell lines examined. The second aim was to synthesize PEG5K-PPMP2 as an amphiphilic prodrug for PPMP and a carrier for other anticancer drugs. PEG5K-PPMP2 was successfully synthesized from Z-D-Ser-OH through a scheme with 12 steps. The products of each steps were confirmed by NMR.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
30 July 2015 |
| Date Type: |
Publication |
| Defense Date: |
29 May 2015 |
| Approval Date: |
30 July 2015 |
| Submission Date: |
29 July 2015 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
48 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Pharmacy > Pharmaceutical Sciences |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Dual-function carriers, micelles, anticancer drugs, PPMP |
| Date Deposited: |
30 Jul 2015 15:15 |
| Last Modified: |
15 Nov 2016 14:28 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/25354 |
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