A lymphocyte-targeting polymeric drug delivery system mediated by receptor-binding epitopes: design, synthesis, and characterization.

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Publication Type dissertation
School or College College of Pharmacy
Department Pharmaceutics & Pharmaceutical Chemistry
Author Tang, Aijun.
Title A lymphocyte-targeting polymeric drug delivery system mediated by receptor-binding epitopes: design, synthesis, and characterization.
Date 2002-12
Description Extensive studies have demonstrated that the use of targetable polymeric drug delivery systems is an efficient approach for improving cancer chemotherapy. In this dissertation, a new strategy for the design of targetable polymeric anticancer drug carriers was proposed that combined water-soluble polymers with epitopes recognizing cell surface receptors. The research investigated the biorecognizability of receptor-binding epitopes presented on structure-simplified peptide templates, and explored the feasibility of transplanting these epitopes to a water-soluble polymer conjugate system for receptor-specific recognition of target cells. The specific objectives of this project were accomplished in three steps. The first step was model establishment. A peptide template containing a nonapeptide epitope as a ligand for B cell CD21 receptor was designed and synthesized by genetic engineering methods. The peptide was immobilized on a solid substrate in an oriented manner and the recognizability of the epitope was evaluated. The results demonstrated the applicability of this model system to display epitopes for biorecognition studies. In the second step, a series of nonapeptide-related peptides were incorporated into a coiled coil stem loop peptide template, and the recognition of these peptides was studied using isolated receptor and receptor-bearing cells. These peptides exhibited varying receptor-binding affinities, thereby revealing their potential as targeting moieties. The last step focused on the synthesis of epitope-containing polymer conjugates and evaluation of their recognizability and cytotoxicity using experimental cell lines. It was found that the epitopes induced specific binding of the conjugates to the target cells and significantly enhanced the cytotoxic activity of polymer-bound doxorubicin. This work describes a potential strategy toward the targeted delivery of anticancer drugs to a subset of lymphocytes for the treatment of lymphoma and leukemia. It is speculated that the combination of water-soluble polymers with receptor-binding epitopes may be applicable to other ligand-receptor systems, and that polymer-based therapeutics can be tailored to specific malignancies.
Type Text
Publisher University of Utah
Subject Pharmaceutical Preparations; Drug Delivery Systems
Subject MESH Neoplasms; Drug Therapy; Chemotherapy, Adjuvant
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "A lymphocyte-targeting polymeric drug delivery system mediated by receptor-binding epitopes: design, synthesis, and characterization." Spencer S. Eccles Health Sciences Library. Print version of "A lymphocyte-targeting polymeric drug delivery system mediated by receptor-binding epitopes: design, synthesis, and characterization." available at J. Willard Marriott Library Special Collection. RS43.5 2002 .T35.
Rights Management © Aijun Tang.
Format Medium application/pdf
Identifier us-etd2,11
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
ARK ark:/87278/s6571sk0
Setname ir_etd
Date Created 2012-04-23
Date Modified 2012-04-23
ID 193143
Reference URL https://collections.lib.utah.edu/ark:/87278/s6571sk0