Biopolymers II

289 Pages·1995·5.56 MB·English

by  A. B. Scranton, B. Rangarajan, J. Klier (auth.), Prof. Nicholas A. Peppas, Prof. Robert S. Langer (eds.)

122 Advances in Polymer Science
Biopolymers II
Guest Editors: N. A. Peppasa nd R. S. Langer
With contributions by
K. S. Anseth, C. L. Bell, C. N. Bowman,
J. Klier, J. Kopecek, A. G. Mikos, S. M. Newman,
N. A. Peppas,D . Putman, B. Rangarajan,
A. B. Scranton,R . C. Thomson, M. C. Wake,
I. V. Yannas,M . J. Yaszemski
With 64 Figures and 10 Tables
Springer
Guest Editors:
Prof. Nicholas A. Peppas
Purdue University, School of Chemical Engineering
West Lafayette, IN 47907- 1283AJSA
Prof. Robert S. Langer
Department of Chemical Engineering,
Institute of Technology,
25 Ames Street, Cambridge, MA 02139AJSA
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Editors
Prof. Akihiro Abe, Department of Industrial Chemistry, Tokyo Institute of Polytechnics,
1583 Iiyama, Atsugi-shi 243-02, Japan
Prof. Henri Benoit, CNRS, Centre de Recherches sur Ies Macromolecules, 6,
rue Boussingault, 67083 Strasbourg Cedex, France
Prof. Hans-Joachim Cantow, Freiburger Materialforschungszentrum,
Stefan Meier-Str. 31a, D-79104 Freiburg i. Br., FRG
Prof. Paolo Corradini, Universim di Napoli, Dipartimento di Chimica, Via Mezzocannone 4,
80134 Napoli, Italy
Prof. Karel Dugek, Institute of Macromolecular Chemistry, Czech Academy of Sciences,
16206 Prague 616, Czech Republic
Prof. Sam Edwards, University of Cambridge, Department of Physics, Cavendisb
Laboratory, Madingley Road, Cambridge CB3 OHE, UK
Prof. Hiroshi Fujita, 35 Shimotakedono-cho, Shichiku, Kita-ku, Kyoto 603 Japan
Prof. Gottfried Glockner, Technische Universith Dresden, Sektion Chemie,
Mommsenstr. 13, D-01069 Dresden, FRG
Prof. Dr. Hartwig Hacker, Lehrstuhl fur Textilchemie und Makromolekulare Chemie,
RWTH Aachen, Veltmanplatz 8, D-52062 Aachen, FRG
Prof. Hans-Heinrich H&hold, Friedrich-Schiller-Universititt Jena, Institut fur Organische
und Makromolekulare Chemie, Lehrstuhl Grganische Polymerchemie, Humboldt&. 10,
D-07743 Jena, FRG
Prof. Hans-Henning Kausch, Laboratoire de Polymkes, Ecole Polytechnique Fed&ale de
Lausanne, MX-D, CH-1015 Lausanne, Switzerland
Prof. Joseph P. Kennedy, Institute of Polymer Science, The University of Akron, Akron,
Ohio 44 325, USA
Prof. Jack L. Koenig, Department of Macromolecular Science, Case Western Reserve
University, School of Engineering, Cleveland, OH 44106, USA
Prof. Anthony Ledwith, Pilkington Brothers plc. R & D Laboratories, Lathom Ormskirk,
Lancashire IA0 SUF, UK
Prof. J. E. McGrath, Polymer Materials and Interfaces Laboratory, Virginia Polytechnic
and State University Blacksburg, Virginia 24061, USA
Prof. Lucien Monnerie, Ecole Superieure de Physique et de Chimie Industrielles,
Laboratoire de Physico-Chimie, Structurale et Macromoleculaire 10, rue Vauquelin,
75231 Paris Cedex 05, France
Prof. Seizo Okamura, No. 24, Minamigoshi-Machi Okazaki, Sakyo-Ku, Kyoto 606, Japan
Prof. Charles G. Overberger, Department of Chemistry, The University of Michigan,
Ann Arbor, Michigan 48109, USA
Prof. Helmut Ringsdorf, Institut fur Organische Chemie, Johannes-Gutenberg-Universitlt,
J.-J.-Becher Weg 18-20, D-55128 Mainz, FRG
Prof. Takeo Saegusa, KRI International, Inc. Kyoto Research Park 17, Chudoji Minamima-
chi, Shimogyo-ku Kyoto 600 Japan
Prof. J. C. Salamone, University of Lowell, Department of Chemistry, College of Pure
and Applied Science, One University Avenue, Lowell, MA 01854, USA
Prof. John L. Schrag, University of Wisconsin, Department of Chemistry, 1101 University
Avenue. Madison, Wisconsin 53706, USA
Prof. G. Wegner, Max-Planck-lnstitut fur Polymerforschung, Ackermannweg 10,
Postfach 3148, D-55128 Mainz, FRG
Preface
Significant developments have occurred in recent years in the fields of biopolymers
and biomaterials. New synthetic materials have been synthesized and tested for a
variety of biomedical and related applications from linings for artifical hearts to
artifical pancreas devices and from intraocular lenses to drug delivery systems. Of
particular interest in the future is the development of intelligent polymers or materials
with special functional groups that can be used either for specialty medical
applications or as templates or scaffolds for tissue regeneration.
In this second volume, following volume no. 107, we have collected review
articles by leading authorities in the field of biomaterials who address the structure,
properties and medical uses of a number of new polymers. All reviews have a strong
emphasis on the polymer aspects of the biomedical development and offer ample
evidence of how the structure can influence the medical behavior of these systems.
We hope that these reviews will become helpful, if not standard, references in
the field and will contribute to our understanding of biopolymers.
December 1994 Nicholas A. Peppas
Robert S. Langer
Table of Contents
Biomedical Applications of Polyelectrolytes
A. B. Scranton, B. Rangarajan, J. Klier . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Polymer Conjugates with Anticancer Activity
D. Putnam, J. Kope~ek . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
Biomedical Membranes from Hydrogels and Interpolymer
Complexes
C. L. Bell, N. A. Peppas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
Polymeric Dental Composites: Properties and Reaction
Behavior of Multimethacrylate Dental Restorations
K. S. Anseth, S. M. Newman, C. N. Bowman . . . . . . . . . . . . . . . . . . . . . . . 177
Tissue Regeneration Templates Based on Collagen-
Giycosaminoglycan Copolymers
I. V. Yannas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219
Biodegradable Polymer Scaffolds to Regenerate Organs
R. C. Thomson, M. C. Wake, M. J. Yaszemski, A. G. Mikos . . . . . . . . . . . 245
Author Index Volumes 101 - 122 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283
Biomedical Applications of Polyelectrolytes
A. B. Scranton 1, B. Rangarajan 1, J. Klier 2
Michigan State University, Depar tment of Chemical Engineering,
East Lansing, MI 48824, USA
2 The Dow Chemical Company, Central Research, Advanced Polymeric
Systems Laboratory, Building # 1712, Midland, MI 48640
Polyelectrolytes are used in a variety of biomedical systems, including dental adhesives and
restorations; controlled release devices; polymeric drugs, prodrugs, and adjuvants; and biocompat-
ible materials. This article provides a review of biomedical applications of polyelectrolytes with
emphasis on recent developments, For completeness, an overview of the methods for polyelectrolyte
synthesis is provided along with a description of the unique properties of polyelectrolyte solutions,
gels, and complexes which make them useful in biomedical applications. The discussion of dental
materials focuses on the recent developments in glass-ionomer cements and novel organic polyelec-
trolyte adhesives since these materials are replacing the traditional zinc carboxylates. The section on
controlled release applications includes a brief overview of recent developments in the mature areas
of coatings, matrices and binders; and provides more in-depth discussions of the advanced respon-
sive, bioadhesive, and liposomal systems that have emerged in recent years. Finally, descriptions of
the recent work in polyelectrolytes as biocompatible materials as well as drugs or prodrugs are
provided.
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2 Synthesis of Polyeleetrolytes . . . . . . . . . . . . . . . . . . . . . . . . . 3
2.1 Polyelectrolyte Synthesis by Polymerization of Ionogenic
Monomers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
2.2 Polyelectrolyte Synthesis by Polymer Modification . . . . . . . . 8
3 Polyelectrolyte Properties . . . . . . . . . . . . . . . . . . . . . . . . . 10
4 Polyelectrolyte-Based Dental Materials . . . . . . . . . . . . . . . . . t4
4.1 Glass-Ionomer Cements - Composit ions and Reactions . . . . . 15
4.2 Adhesion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
4.2.1 Organic-Polyelectrolyte Adhesives . . . . . . . . . . . . . 19
4.2.2 Glass-Ionomer Adhesives . . . . . . . . . . . . . . . . . . 21
4.3 Glass-Ionomer Cements - Performance . . . . . . . . . . . . . . 22
4.3.1 Marginal Leakage . . . . . . . . . . . . . . . . . . . . . . . 22
4.3.2 Tissue and Pupal Responses . . . . . . . . . . . . . . . . 23
4.3.3 Controlled Release from Dental Materials . . . . . . . . 23
1 Authour to whom correspondence should be sent
Advancesi n PolymerS cience,V oL 122
© Springer-VeflagB erlinH eidelberg1 995
2 A.B. Scranton et al.
Controlled Release Applications of Polyelectrolytes . . . . . . . . . . . 24
5.1 Polyelectrolytes in Controlled Release Coatings, Matrices,
and Binders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
5.2 Polyelectrolytes in Novel Responsive Delivery Systems . . . . . 30
5.3 Polyelectrolyte Bioadhesive Delivery Systems . . . . . . . . . . 33
5.4 Liposome Controlled Release Systems . . . . . . . . . . . . . . . 35
6 Polymeric Drugs, Prodrugs and Adjuvants . . . . . . . . . . . . . . . . 37
7 Polyelectrolytes as Biocompatible Materials . . . . . . . . . . . . . . . 39
8 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
Biomedical Applications of Polyelectrolytes
1 Introduction
Polyelectrolytes are polymers which contain relatively high concentrations of
ionizable groups along the backbone chain. Polyelectrolytes are distinguished
from a related class of polymers, ionomers, by the density of the ionizable
groups. Ionomers contain a relatively low concentration of ionizable groups
(less than a few mole % of repeating units) while polyelectrolytes contain
ionizable groups at levels ranging anywhere from a few mole % to 100 of the
repeating units. Polyelectrolytes may be anionic, cationic, or amphophilic, and
may be synthetic or naturally occurring. Examples of common polyelectrolytes
include polymeric acids such as poly(acrylic acid) and poly(methacrylic acid),
polymeric bases such as poly(vinyl amine) and poly(4-vinyl pyridine), and many
naturally occurring proteins, polysaccharides, and nucleic acids.
The unique properties exhibited by polyelectrolytes have lead to their
application in biomedical systems. Many biomedical applications of poly-
electrolytes ultimately arise from their propensity to bind with oppositely
charged surfaces and to associate to form complexes with oppositely charged
polymers. For example, cationic polyelectrolytes have long been studied for
their application in silicosis therapy and immunochemistry due to their ability
to bind with negatively charged surfaces, and cationic polyelectyrolytes such as
poly(vinyl pyridine N-oxide) are potent inhibitors of silica hemolysis of red
blood cells. Similarly, complexes composed of two oppositely charged polyelec-
trolytes have been extensively employed as enteric coatings and controlled
release devices, and many polyelectrolytes and their complexes have exhibited
an antithrombogenic character.
This contribution will provide a review of polylectrolytes as biomaterials,
with emphasis on recent developments. The first section will provide an over-
view of methods of synthesizing polyelectrolytes in the structures that are most
commonly employed for biomedical applications: linear polymers, crosslinked
networks, and polymer grafts. In the remaining sections, the salient features of
polyelectrolyte thermodynamics and the applications of polyelectrolytes for
dental adhesives and restoratives, controlled release devices, polymeric drugs,
prodrugs, or adjuvants, and biocompatibilizers will be discussed. These topics
have been reviewed in the past, therefore previous reviews are cited and only the
recent developments are considered here.
2 Synthesis of Polyelectrolytes
Polyelectrolytes are synthesized by incorporating ionogenic functional groups
into a polymer chain or by attaching oligomeric grafts which extend from the
backbone chain. Moreover, the ionogenic groups may be introduced into the
4 A.B. Scranton et al.
polymer chain at the time of synthesis by (co)polymerization of ionogenic
monomers or may be added by chemical modification or functionalization of
existing polymers. The first approach is generally more versatile and more
commonly employed since the structure and properties of the final polyelec-
trolyte may be largely controlled through the composition of the reaction
mixture or the reaction conditions. However, the method of choice for a particu-
lar application depends largely upon the type of ionogenic functional group to
be added and the nature of the parent polymeric chain. For example, the
post-functionalization approach is often employed for the synthesis of graft
polyelectrolytes or for modification of natural polymers such as tignin. In this
paper, an overview of the methods for synthesis of polyelectrolytes will be
presented, including examples of the variety of synthetic schemes that have been
developed. However, because the focus of this review is biomedical applications
of polyelectrolytes the discussion presented here will be representative rather
than exhaustive. Methods based upon polymerizations of ionogenic monomers
will be considered first, followed by methods based upon chemical modification
of existing polymers.
2.1 Polyelectrolyte Synthesis by Polymerization of lonogenic
Monomers
Polyelectrolytes are most commonly synthesized by free-radical chain polym-
erizations of ionogenic "monomers containing a carbon double bond. The
well-established mechanism for free radical polymerizations is described in
many general polymer texts [1-3]. Polymerization begins when an initiating
species produces active radical centers, typically by homolytic dissociation of
a weak bond or by a redox reaction. Once formed, the active radical centers
rapidly propagate through the carbon double bonds of many monomer units to
form polymer chains. When two active radical centers meet, they may react with
one another by combination or disproportionation to terminate the polymeriz-
ation process. This free radical reaction scheme is very versatile and may be
employed to produce polyelectrolytes in a variety of structures. Crosslinked
polymeric structures may be readily produced by including small quantities
(typically less than 1 mole %) of a divinyl crosslinking agent which may partici-
pate in the propagation of two radical chains and may therefore produce
a crosslink between chains.
Many ionogenic monomers containing a polymerizable carbon double bond
have been reported in the literature, and therefore a wide variety of anionic,
cationic, and amphophilic polyelectrolytes may be synthesized using free radical
polymerizations. Examples of anionic ionogenic monomers which have been
used to synthesize anionic polyelectrolytes include acrylic acid [4-10], methac-
rylic acid 1"6-8, 11, 12], sodium styrenesulfonate [7, 13, 141, p-styrene carboxylic