Polymeric Materials in Medication

300 Pages·1985·11.31 MB·English

by  Charles G. Gebelein (auth.)

POLYMERIC
MATERIALS
IN MEDICATION
POLYMER SCIENCE AND TECHNOLOGY
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Edited by Charles G. Gebelein and Charles E. Carraher, Jr.
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POLYMERIC
MATERIALS
IN MEDICATION
EDITED BY
CHARLES G. GEBELEIN
Youngstown State University
Youngstown, Ohio
AND
CHARLES E. CARRAHER, JR.
Florida Atlantic University
Boca Raton, Florida
Springer Science+Business Media, LLC
Library of Congress Cataloging in Publication Data
Main entry under title:
Polymeric materials in medication.
(Polymer science and technology; v. 32)
Proceedings of a symposium held Aug. 26-31, 1984, in Philadelphia, Pa.
Includes bibliographies and index.
1. Drugs—Controlled release—Congresses. 2. Polymers and polymerization-
Therapeutic use—Congresses. I. Gebelein, Charles G. II. Carraher, Charles E. III.
Series. [DNLM: 1. Dosage Forms—congresses. 2. Polymers—therapeutic use-
congresses. QV 785 P77834 1984]
RS201.C64P65 1985 615M9 85-25671
ISBN 978-1-4899-2247-2
ISBN 978-1-4899-2247-2 ISBN 978-1-4899-2245-8 (eBook)
DOI 10.1007/978-1-4899-2245-8
Based on the proceedings of a symposium on Polymeric Materials in Medication,
held August 26-31, 1984, in Philadelphia, Pennsylvania
© 1985 Springer Science+Business Media New York
Originally published by Plenum Press, New York in 1985
Softcover reprint of the hardcover 1st edition 1985
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
PREFACE
The art of using chemical agents for medication dates back into
antiquity, although most of the earliest examples used plants, herbs, and
other natural materials. The old Egyptian medical papyri, which date from
before 1400 B.C., contain dozens of examples of such medicinal plants and
animal extracts. In the Old Testament of the Bible, we can find
references to using oil to soften the skin and sores (Isaiah 1:6), the
use of tree leaves for medicine (Ezekiel 47:12) and various medical balms
(Jeremiah 8:22). Not all these recipes were effective in curing the
ailments for which they were used and sometimes the treatment was worse
than the disease. Nevertheless, the art of using chemical derived agents
for medicines continued to develop and received great impetus during the
present century with the rise of synthetic organic chemistry.
One of the most vexing problems has always been to achieve specifici
ty with the medications. While some medical agents do indeed possess a
relatively high degree of specificity, most agents are far more systemic
than would be desired. Much of the research efforts to correct this
deficiency has centered on modifying the chemical agents themselves.
Unfortunately, there are severe limitations in this approach since minor
modifications often drastically affect the therapeutic activity and can
even render the drug completely ineffective, or worse. Frequently the
choice must be made between using a medication, with all it's attendant
toxic side effects, or having the disease rage rampant in the patient.
The use of polymeric materials to mediate medications is of fairly
recent vintage. There are several distinctive ways in which polymers have
been tried in medication and most of these ways are covered to some
extent in this book. Because these different methods often interrelate
with each other, we have chosen not to subdivide this book into seperate
sections dealing with specific approaches to this general problem. The
book does, nevertheless, have a particular plan of attack.
The first chapter is a general survey (Gebelein) and is followed by a
chapter considering how polymeric materials interact with the body tis
sues (Marchant & Anderson). The next six chapters (Chien; Dunn, et al,
Gaskill, et al; Ragunthan, et al; Lee; Balazs, et al) are mainly con
cerned with controlled release systems in a variety of medical applica
tions. The use of polymers with potential utility in cancer treatment
comprise the next seven chapters (Ghosh & Maiti; Hartsough & Gebelein;
Alderfer, et al; Baldwin, et al; Giron, Espy & Carraher; Giron, et al;
Carraher, et al). Some of these involve bioactive polymers while others
involve controlled release systems. The following three chapters consider
the use of polymers to solubilize medicines (Pitha), some osmium con
taining polymers (Hinckley), and the use of various polymers) to stimu
late the production of interferon (Hodnett), a natural bioactive poly
mer. The last three chapters (Samanen; Saraswathi & Keyes; Hudecz, et al)
v
are concerned with various aspects of proteins as polymeric medications.
The Editors wish to thank the individual authors for their fine
contributions. We also acknowledge the excellent support of the American
Chemical Society Division of Polymeric Materials: Science and Engineering
who sponsored the original symposium at the National A.C.S. meeting in
Philadelphia, PA, in August, 1984. Last, but definitely not least, the
authors wish to thank their families for their special support and
encouragement during the preparation of this book.
Charles G. Gebelein
Polymer and Biomaterials Laboratory
Youngstown State University
Youngstown, Ohio 44555
and
Charles E. Carraher, Jr.
Dean of Science
Florida Atlantic University
Boca Raton, Florida 33432
CONTENTS
Methodologies in Polymeric Medication 1
C. G. Gebelein
Tissue/Material Interactions of Biomedical Polymers 11
R. E. Marchant and J. M. Anderson
Polymer-Controlled Drug Delivery Systems: Science and Engineering 27
Y. W. Chien
Fibrous Delivery Systems for Antimicrobial Agents 47
R. L. Dunn, J. W. Gibson, B. H. Perkins, J. M. Goodson
and L. E. Laufe
Evaluation of Membrane Suitability in Transdermal Drug Delivery 61
J. L. Gaskill, P. P. Sarpotdar and R. P. Giannini
Diffusion Controlled Release of Drugs from Coated Drug
Polymer Complex 73
Y. Raghunathan, L. Amsel, o. Hinsvark, K. Rotenberg
Kinetics of Drug Release from Glassy Polymers: Effect of
Initially Nonuniform Drug Distribution 79
P. I. Lee
The Role of Polymer Matrix Structure and Interparticle
Interaction in Diffusion-Limited Drug Release 87
A. C. Balazs, D. F. Calef, J. M. Deutch, R. A. Siegel
and R. Langer
Polymeric Anticancer Agents - An Overview 103
M. Ghosh and S. Maiti
The Controlled Release of 5-Fluorouracil from Acrylate Copolymers
of 1-(N-2-Ethylmethacrylcarbamoyl)-5-Fluorouracil Monomer 115
R. R. Hartsough and C. G. Gebelein
Halogenated Nucleic Acids: Biochemical and Biological Properties
of Fluorinated Polynucleotides 125
J. L. Alderfer, R. E. Loomis, S. D. Soni, M. Sharma,
R. Bernacki and R. Hughes, Jr.
Toxicity and Tissue Distribution of MVE-2 in the Dog After
Intravenous and Intraperitonal Administration 139
J. R. Baldwin, R. A. Carrano, A. R. Imondi, J. D. Iuliucci
and L. M. Hagerman
Transformation of Mouse Fibroblast (T3T) Cells Employing the
Oncogenic Simian Virus 40 (SV40) for Evaluation of
Anticancer Compounds 151
D. J. Giron, M. J. Espy and C. E. Carraher, Jr.
Screening of Platinum II Polymines as Antitumor Drugs Employing
Cell Differation of Normal and Transformed 3T3 Cells 165
D. J. Giron, M. J. Espy, C. E. Carraher, Jr., and I. Lopez
Polymeric Derivatives of cis-Dichlorodiammineplatinum II Analogs
Based on Polyvinylamine-co-vinylsulfonate as Model Carriers
In the Drug Delivery Systems. 173
C. E. Carraher, Jr., C. M. Ademu-John, J. J. Fortman,
D. J. Giron, C. Turner and R. Linville
Soluble Excipients Assisting Dissolution of Drugs: Importance
of Amorphous State 183
J. Pitha
Polymeric Hydroxamic Acids for Iron Chela tors Therapy 191
A. Winston, D. V. P. R. Varaprasad, J. J. Metterville and
H. Rosenkrantz
Oxygen Species Chemistry of Osmium Carbohydrate Polymers 197
C. C. Hinckley, K. A. Islam and P. A. Kibala
Synthetic Polymeric Inducers of Interferon 211
E. M. Hodnett
Polypeptides as Drugs 227
J. M. Samanen
A Systematic Approach to Induce New Catalytic Activities
in Proteins 249
S. Saraswathi and M. H. Keyes
Branched Polypeptides with a Poly(L-Lysine) Backbone: Synthesis,
Conformation, and Immunomodulation 265
F. Hudecz, H. Votavova, D. Gaal, J. Sponar, J. Kajtar, K.
Blaha and K. Szekerke
Contributors 291
Index 297
viii
METHODOLOGIES IN POLYMERIC MEDICATION
Charles G. Gebelein
Polymer and Biomaterial Laboratory
Department of Chemistry
Youngstown State University
Youngstown, Ohio 44555
The range of polymeric systems that can be used in
medication is discussed. These approaches include controlled
release devices (such as erodable systems, diffusion control
led systems, mechanical systems and microcapsules), biolo
gically active polymers (such as natural polymers, synthetic
polypeptides, pseudo-enzymes, pseudo-nucleic acids and poly
meric drugs), and immobilized bioactive materials (such as
immobilized enzymes, antibodies and other bioactive agents).
Some illustrations of these methodologies are presented.
INTRODUCTION
The major purpose of this paper is to define and to illustrate the
term "polymeric medication" and to serve as an introduction to the theme
of this book. For our purposes, the term polymeric medication would
include any system that would utilize any type of polymeric material to
make medication more effective. No attempt is made here to be encyc
lopedic in scope or exhaustive in documentation. This area is too varied
and the number of papers is too large for this to be possible in this
short overview. Some of the topics introduced in this chapter will be
considered in more detail in subsequent chapters in this book.
CLASSES OF POLYMERIC MEDICATION SYSTEMS
Polymeric medication will be subdivided into three areas in this
chapter:
(a) Controlled Release Systems
(b) Biologically Active Polymers
(c) Immobilized Bioactive Materials
Naturally, there will be some overlap between these areas, but this
will occur in any system of division. Each of these major categories will
be further subdivided into more specific areas for the convenience of
discussion. A more complete discussion of these categories has been
published previously (1).