2000 McCoy Award Recipient
Nicholas A. Peppas
Professor Biomedical Engineering

Professor Nicholas A. Peppas, Showalter Distinguished Professor of Biomedical Engineering, was presented the prestigious Herbert Newby McCoy Award during the University Honors Convocation held April 14, 2000, for contributions to science for his research on therapeutic formulations for protein and drug delivery.

Professor Nicholas A. Peppas is the Showalter Distinguished Professor of Chemical and Biomedical Engineering of Purdue University. He has been at Purdue since 1976 and holds joint appointments in the School of Chemical Engineering and the new Department of Biomedical Engineering, which he helped found. In addition, he is the Director of the National Science Foundation Program on Therapeutic and Diagnostic Devices, an innovative educational, training and research program formed wit h the support of NSF in 1999 and spanning seven different schools and departments in the Lafayette and Indianapolis campus.

Peppas was educated in chemical engineering at the National Technical University of Athens, Greece (Dipl.Eng., 1971) and at the Massachusetts Institute of Technology (Sc.D., 1973). In addition to his Purdue appointment, he has served as a Visiting Professor at the Universities of Geneva (Switzerland), Paris XIII (France), Parma (Italy), Naples (Italy), Pavia (Italy), Hoshi (Tokyo, Japan), Hebrew (Jerusalem, Israel) and the California Institute of Technology. In 2001, he will be a Visiting Professor at the Free University of Berlin (Germany), and at the University of Santiago de Compostela and the Complutense University of Madrid (Spain).

His research contributions cover a wide range of fundamental studies in macromolecular science, drug delivery, biomedical polymers, mass transfer, polymerization kinetics and biomedical engineering. His group has contributed to the dynamics of macromolecular chains in dilute and semi-dilute solutions, as well as to the behavior of complex macromolecular chains in contact with biological surfaces. He is internationally known for his work on the preparation, characterization and evaluation of the behavior of a class of crosslinked polymers known as hydrogels, which have been used as biocompatible materials and as carriers in controlled delivery of drugs, peptides and proteins.

Peppas' work does not only address the fundamentals of his field but has also found a wide range of applications in the biomedical field. His group pioneered the use of hydrogels in drug delivery applications, including epidermal bioadhesive systems and systems for the release of theophylline, proxyphylline, diltiazem, and oxprenolol. Upon study of the critical behavior of intelligent polymers, Peppas and his group were the first to employ such pH-sensitive and temperature-sensitive systems for modulated release of streptokinase and other fibrinolytic enzymes. His group has also developed novel transmucosal controlled release devices. More recently, his group has announced new inventions of oral insulin delivery systems and new biomaterials. Peppas' group has also invented new materials for hard, oxygen-permeable contact lenses, and for reconstruction of vocal cords.

In recognition of his research accomplishments he has received honorary doctorates from the University of Ghent (Belgium, 1999), the University of Parma (Italy, 1999), and the University of Athens (Greece, 2000).

Peppas is the co-author or coeditor of 25 books and volumes, and the author of 650 publications, 280 proceedings papers and preprints, 200 abstracts and 10 patents. He is one of the most cited scientists in the world according to the recent ISI survey of most cited authors for the period 1981- June 1997. Since 1982, he has been the editor of the premier Journal in his field, Biomaterials. Since 1998 he has been one of the editors of Advances in Chemical Engineering.

Peppas has been recognized by more than 60 awards including the 2000 General Electric Senior Research Award of ASEE recognizing the best engineering researcher of the USA,; the 1999 Research Achievement Award in Pharmaceutical Technology of the American Association of Pharmaceutical Scientists,; the 1995 APV-International Pharmaceutical Technology Medal,; the 1994 Food, Pharmaceutical and Bioengineering Award of the American Institute of Chemical Engineers,; the 1992 Clemson Award for Basic Research of the Society for Biomaterials,; the 1992 George Westinghouse Award of ASEE,; the 1991 Founders Award for Outstanding Research from the Controlled Release Society,; the 1988 Curtis McGraw Award of ASEE for best ngineering research under the age of 40,; and the 1984 Materials Engineering and Sciences Award of the American Institute of Chemical Engineers.

Peppas has been elected a Founding Fellow of the American Institute of Medical and Biological Engineering (1993), a Fellow of the American Association of the Advancement of Science (2000), a Fellow of the American Physical Society (1997), a Fellow of the American Institute of Chemical Engineers (1997), a Fellow of the Society for Biomaterials (1994), a Fellow of the American Association of Pharmaceutical Scientists (1993) and an Honorary Member of the Italian Society of Medicine and Natural Sciences (1996). In 1991 he was named a Polymer Pioneer by Polymer News. He has supervised the theses of 45 Ph.D. students, including 20 current professors in other Universities, and another 70 students, postdoctoral fellows and visiting scientists.

Abstract of talk
Novel complexation copolymer networks of poly(methacrylic acid) grafted with poly(ethylene glycol) have been shown to be excellent carriers for proteins due to their pH-sensitive swelling behavior as a result of the formation of reversible interpolymer complexes stabilized by hydrogen bonding between the carboxylic acid protons and the etheric groups on the grafted chains. Additionally, the presence of the PEG grafts stabilizes entrapped peptides and proteins. Because of the complexation phenomena in these networks, the characteristic mesh size in these gels is an order of magnitude greater in the uncomplexed state than in the complexed state. Because of their oscillatory swelling behavior, these gels can be used as oral carriers for insulin and calcitonin where the release of the bioactive agent in the intestine is preferable. Upon oral administration of insulin loaded gels, the blood glucose levels in rats were significantly reduced due to release of insulin in the upper small intestine. Recent studies with nanoparticles of these gels in contact with CaCo-2 cells indicate lack of cytotoxicity and improved permeability by paracellular transport.

Micropatterning and molecular imprinting using such intelligent biopolymers are powerful techniques for the preparation of films with highly specific molecular recognition capabilities. The importance of these techniques is related to the characteristics of molecular recognition. Recognition is provided by various groups that govern the specificity and affinity of biological molecules for other compounds. Molecularly imprinted polymers (MIP's) have the same type of recognition as spatially distinct functional groups, i.e. synthetic counterparts to biological molecules. MIP's possess "cavities" with high specificity and binding affinity for the template molecule, recognized by non-covalent, covalent or metal coordination interactions. A high amount of cross-linking provides the required rigidity of the structure. We have developed several approaches for the preparation of MIPs. Most of our studies have been with the non-covalent approach, where the interaction between monomers and template is achieved by various non-covalent interactions such as hydrogen bonding, ionic or electrostatic interactions. The clear advantage of this technique is the ease of preparation of the polymers. The monomers and template are simply mixed together and allowed to interact based on the idea of "self-assembly". The disadvantages of this approach include the equilibrium-governed nature of the interactions and the possibility of the creation of unfavorable binding sites.

The idea of patterning the properties and surfaces at the molecular level is of extreme interest for controlling the adsorption of proteins and the attachment of cells for applications in biosensors and tissue engineering. Micropatterns aid the adsorption process tremendously by allowing for very selective adhesion.

Research
Peppas joined Purdue in 1976 and established an internationally recognized program in polymers, biomaterials and drug delivery. His contributions have been in polymers, biomedical engineering, biomaterials, drug delivery, mass transfer, kinetics and reaction engineering.

His polymer research has examined fundamental aspects of the thermodynamics of polymer networks in contact with solvents, the conformational changes of networks under load or in the presence of a solvent, the anomalous transport of liquids in glassy polymers, and the kinetics of fast UV-polymerization reactions. This work easily explains most aspects of gaseous diffusion.

In the field of polymer science, Peppas investigated the effects of polymer structural characteristics on the diffusion coefficient and diffusion behavior of small and large molecules, concentrating on the diffusion of liquid penetrants and macromolecules through glassy and rubbery polymers in the presence or absence of macromolecular relaxations. He developed exact molecular and approximate phenomenological theories for describing such systems. He developed new molecular theories that account for the effect of the macromolecular structure of polymers on its solute diffusion coefficient. For example, Peppas introduced two theories that can predict the dependence on the number average molecular weight between crosslinks, the hydrodynamic radius of the solute, and the degree of swelling for highly and moderately swollen nonporous membranes. Along with Prof. Caruthers, he developed necessary and sufficient conditions for Fickian and non-Fickian diffusion of a solute through glassy swellable polymers. Their continuum thermodynamic theory to describe anomalous transport in glassy polymers is a classic paper in the literature, and the experimental verification of this model has led to its wide applicability in the field.

In addition, Peppas has investigated polymer-polymer interdiffusion and provided important physical interpretation of adhesion and healing phenomena. This work has yielded models and experimental studies of systems important in controlled-release applications. He investigated gaseous diffusion through rubbery and semicrystalline polymers and through glassy polymers where gaseous solubility in the polymer is progressively altered by changing the structure of the glassy copolymer. His fundamental studies illuminated the nature of hydrogen bonding in complexation hydrogels, crystallization of polymers, rubber elasticity of networks, structure of crosslinked polystyrene, structure of polymerldiluent systems, and block copolymers. He performed significant work on the polymerization kinetics of acrylates and methacrylates, especially multifunctional monomers used in producing networks. Peppas has studied the preparation and properties of highly crosslinked polymers, which can be used in such high-tech applications as coatings, films, optical fibers, compact disks, and lenses. He developed fundamental descriptions for the propagation and termination rate constants of multifunctional polymerization/crosslinking reactions.

Peppas' research accomplishments in bioengineering include investigation of the surface properties of hydrogels in relation to medical applications and applied such systems to the development of materials for articular cartilage, vocal cords, contact lenses, artificial kidney membranes, and artificial organs in general. Peppas performed pioneering work in developing biomedical surfaces for a portable artificial kidney and for systems to treat thrombotic effects defects through the use of streptokinase form from fibrinolytic enzymeimmobilized microparticles. He showed that diffusional effects play an important role in protein adsorption on polymeric surfaces for biomedical applications. He developed, with his research group, new biomaterials based on methacrylates, acrylates, polyvinyl alcohol) and polyethylene glycol). The research group has shown that the pH-sensitivity of many of these systems can be used to develop intelligent biomedical devices and biosensors. Finally, he contributed to our understanding of biomedical transport and interfacial phenomena, from the study of arteriosclerosis to solute transport in mucus and transport in bioadhesion.

Peppas is also a leading authority on therapeutic formulations for protein and drug delivery. He is internationally known for his work on preparing, characterizing, and evaluating the behavior of compatible, crosslinked polymers known as hydrogels, which have been used as biocompatible materials and in controlled release devices, especially in controlled delivery of drugs, peptides, and proteins, development of novel biomaterials, biomedical transport phenomena, and biointerfacial problems. In drug delivery, Peppas originated and is the leading proponent of the use of hydrophilic polymers and hydrogels for the controlled delivery of drugs, peptides, and proteins. He developed the new class of "swelling-controlled release systems," which exhibit an unexpected time-dependent (zero-order) release due to coupling of diffusional and relaxational mechanisms. Peppas and his students were the first to propose and solve complex transport equations incorporating the viscoelastic behavior of the polymer and its relaxational behavior during swelling and drug release. He also introduced two dimensionless numbers, the Swelling Interface number (Sw) and the Swelling Area number (Sa), used by researchers in the discipline. He proposed the now well-known exponential time dependence of the quantity of drug released, which has become a most desirable equation for the analysis of non-Fickian drug delivery.

Peppas also developed and tested, with his students, systems for release of vasodilators such as theophylline and proxyphilline, beta-Mockers blockers such as oxprenolol and anti-inflammatory agents such as metronidasole. He has made seminal contributions to the understanding of release from pH-sensitive and temperature-sensitive swelling systems. In collaboration with colleagues he described the characteristics of pH-sensitive delivery, analyzed the oscillatory behavior using Bolzman superposition analysis, showed the influence of ionic strength and buffer composition on controlled release, and developed new delivery systems. Of particular interest is the work on insulin delivery using pH- and temperature-sensitive release systems. He and his research group made exceptional contributions to the development of novel mucoadhesive systems for targeted delivery.