Campus Access Only

All rights reserved. This publication is intended for use solely by faculty, students, and staff of University of the Pacific. No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, now known or later developed, including but not limited to photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author or the publisher.

Date of Award


Document Type

Dissertation - Pacific Access Restricted

Degree Name

Doctor of Philosophy (Ph.D.)


Pharmaceutical and Chemical Sciences

First Advisor

Xiaoling Li

First Committee Member

Bhaskara Jasti

Second Committee Member

David Thomas

Third Committee Member

William Chan

Fourth Committee Member

Patrick Jones


Targeted drug delivery is desired in cancer therapy since most of the side effects common to chemotherapy are related to the toxicity of the drug. Integrin over-expression has been shown in various cancer cells and can be exploited for targeted drug delivery. The goal of this study is to design amphiphilic conjugates with targeting motifs as a targeted drug delivery carrier. Toward this effort, novel amphiphilic conjugates of the Arg-Gly-Asp (RGD) peptide or GRGDS was linked to aliphatic acids of varying chain length. The hypothesis is that these novel amphiphilic conjugates, at concentrations above the critical micelle concentration (CMC), can form micelles in aqueous environment, encapsulate poorly-water soluble drugs, and target the α v β 3 integrin. The amphiphilic conjugate is also hypothesized to serve as targeting moiety in mixed micelle drug delivery system using Pluronic block copolymer. Synthesis of RGD amphiphilic conjugates was achieved by converting carboxylic acids into more reactive N-hydroxysuccinimidyl derivative and converting the carboxylic functional group of peptide into methyl ester. Then the activated NHS aliphatic ester was conjugated with methyl-protected peptide in the presence of organic base and methyl ester was removed in NaOH and subsequently neutralized. Intermediates and final products were characterized by MS, FTIR, and NMR. Micelle formation occurred in concentration of 0.015 to 0.12 mM for C 14 -RGD, C 16 -RGD, C 18 -RGD, and C 18 -GRGDS. Amphiphilic conjugate mixed with Pluronic L121 and Pluronic P104 (5% C 18 -RGD/L121 and 10% C 18 -GRGDS/P104) formed micelles at lower CMC of 0.0006 and 0.01 mM, respectively. Solubility of Taxol in water was improved by 87% when encapsulated in C 18 -RGD micelle above CMC. The solubility was increased 7 fold and 18 fold in mixed micelles of 5% C 18 -RGD/P104 and 5% C 18 -RGD/L121 above CMC. Three different drugs (DOX, Taxol, and etoposide) were used to evaluate the efficacy of the targeting C 18 -GRGDS micelle carrier alone or C 18 -RGD mixed with Pluronic block copolymers micelle. All 3 drugs significantly enhanced cytotoxicity toward cancer cells when loaded in micelle carrier above CMC. With same DOX concentration, C 18 -GRGDS micelle carrier significantly decreased percent of viable cells (12.9 ± 1.2%) above CMC when compared to concentrations below CMC (24.1 ± 1.0%). Mixed micelle of targeting amphiphile and Pluronic loaded with Taxol above CMC significantly decreased the percent of viable cells (38.3 ± 7.9%) when compared to non-targeting Pluronic block copolymer micelle (56.0 ± 2.8%). (Abstract shortened by UMI.)



To access this thesis/dissertation you must have a valid email address and log-in to Scholarly Commons.

Find in PacificSearch Find in ProQuest



If you are the author and would like to grant permission to make your work openly accessible, please email


Rights Statement

Rights Statement

In Copyright. URI:
This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).