Polymeric Biomaterials As Enzyme and Drug Carriers* Part I: Immobilization of Enzymes

Abstract

INTRODUCTIONhe immobilization of drugs and enzymes refers to their attachment to solid supports. In many cases, the immobilized materials remain biologically active and can be used in numerous research investigations. The basic idea in immobilizing drugs or enzymes on solid supports is to control the gross movement of the immobilized material relative to that of the support. In most cases, the immobilized compounds can still undergo conformational changes. If the compound is connected to the support through a spacer arm, then the compound can move several Angstroms or micrometers relative to the support. However, the actual freedom of movement of immobilized materials depends on several factors, including (1) the type of immobilization chemistry employed, (2) the presence of interactions with the support and (3) the use of single or multiple points of attachment, as well as crosslinking between points on the immobilized material or between the immobilized material and the support.Several chemical techniques, plus many more variations, have been described for the immobilization of biochemicals on solid supports. These include trapping in gels or polymeric matrices, adsorption on surfaces, covalent attachment to organic and inorganic surfaces, and encapsulation in liposomes or other small vesicles [1,2]. *This is the first of a four-part review. Downloaded from 244The current interest in the immobilization of enzymes grew out of the early studies by Manecke [3] in Germany and Katchalski [4] in Israel in the early 1960s, for coupling enzymes and antibodies to polymeric supports. A few years later, natural hormones (adreno-corticotropic hormone, insulin) were covalently coupled to agarose beds and tested for biological activity against isolated mammalian cells [5,6].Many other compounds have been immobilized on solid supports in the intervening years, so that by 1990 it is estimated that over 500 different enzymes may be obtained.In recent years, the use of synthetic polymers as polymeric drugs or drug delivery systems has received increasing attention. Several symposia were organized to discuss the current state-of-the-art research in polymeric drugs [7], controlled release of bioactive materials [8,9] and the general biomedical applications of polymers [10,11]. Studies have largely been confined either to the development of sustained-release systems based on insoluble polymers [12] or to the development of polymeric drugs [7], i.e. soluble polymers which themselves display pharmacological activity. Up to now, more than 100 different drugs have been immobilized on bio-or non-biodegradable polymers.Fewer results have been published on the immobilization of pesticides and fertilizers [13][14][15][16][17][18].

Heparin, Heparinoids, Synthetic Polyanions, and Anionic Dyes

“…The demonstrations of this were made by Adams et al (139) with heparin, dextran and laminarin sulfate induction of osteoporosis. Polyethylene sulfonate, which has similar properties, increases alkaline phosphatase levels (24). In this regard as mentioned previously, it is of interest that the ethylene maleic anhydride copolymer carbetimer, now in clinical anti tumor study, produces hypercalcemia (25).…”

“…Dumitriu et al (24) have reviewed the literature regarding enzyme and drug carriers linked to polymers which have growing validity when applied to direct regional intratumoral injection for local control (12.13.18-22.25).…”

Catalase Immobilized on Poly(Acrylic Acid-co-Vinyl Alcohol)

“…The advantages of employing enzymes immobilized on various supports -especially macromolecular ones -are well known, and they have been discussed in several studies [1][2][3]. When the support utilized is a polymeric one, biocatalyst's bonding may be achieved by several methods, which may be classified into 3 main groups, as follows [4]: -crosslinking -encapsulation -chemical (ionic, covalent) bonding.…”