78 Steps Health Journal

Immobilized Enzymes for Biomedical Applications

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Amaia Esquisabel, Rosa María Hernández, Alicia Rodríguez Gascón, and José Luis Pedraz

Summary

Immobilized enzymes were first applied in the biomedical field aiming to detect bioactive substances or to treat a disease condition. This chapter presents two approaches used for the immobilization of l-asparaginase intended for the treatment of leukemia, based on the entrapment of this enzyme in a matrix. The particulate drug carriers described in this chapter are liposomes and nanoparticles, even though the methods described here could be used for the immobilization of other enzymes with therapeutic uses.

Key Words: Immobilization; l-asparaginase; liposomes; nanoparticles. 1. Introduction

The study of immobilized enzymes for biomedical applications started in the 1960s (1), aiming to solve some of the limitations to the use of enzymes in clinics, to make them more stable, less immunogenic and toxicologic, and to present a longer in vivo circulation lifetime (2). Since then, several approaches have been used in enzyme therapy either for the detection of bioactive substances in the diagnosis of diseases or with the aim to treat a disease condition, such as the correction of inborn metabolic defects, cardiovascular diseases, cancer, intestinal diseases, or for the treatment of intoxication (Table 1).

For the immobilization of enzymes two different approaches have been used (26), the first consisting in the cross-linking or the covalent attachment of the enzyme to a support (immobilization by binding) and the second based on the entrapment of the enzyme in a matrix (immobilization by inclusion).

Among the methods used for immobilization by binding, conjugation with polymers has received great attention in the last several years. A large number of polymers can be considered for enzyme immobilization, although the strict requirements needed for a biomedical approach limit this number significantly. The polymers used for enzyme immobilization may be fully biocompatible, and

Table 1

Enzymes That Have Been Immobilized for a Clinical Purpose

Enzymes That Have Been Immobilized for a Clinical Purpose

Table 1

Enzyme	Disease treated	Ref.
Alcohol dehydrogenase	Alcohol intoxication	3,4
and acetaldehyde

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