Abstract

Background: L-asparaginase is a drug of choice in the treatment of Hodgkin's lymphoma and acute lymphoblastic leukemia. Production of its bioconjugates can increase its half-life, stability and decrease its immunogenicity.

Objective: The aim of the present study was to immobilize this drug on silica nanoparticles by two different cross-linking agents.

Method: The drug was conjugated to nanoparticles by two cross-linking agents; 1-ethyl-3-(3- dimethylaminopropyl) carboiimide HCl (EDC) or glutaraldehyde. The effect of the drug to the nanoparticles ratio, the amount of cross-linking agents and the time of conjugation were optimized according to the zeta potential, size particle and the enzyme immobilization efficiency. Conjugation of L-asparaginase to nanoparticles was confirmed by FT-IR and TEM. The activity, kinetic profiles, stability against pH changes, thermal and storage stability of the native and immobilized drug were compared.

Results: The results showed significant increase in pH range of the stability and decrease in the km value of the drug after immobilization; indicating an increase in the enzyme tendency for the substrate. The Time of stability of the drug increased after immobilization in plasma and phosphate buffer saline which can increase its half-life of circulation.

Conclusion: The activity and stability of immobilized drug by EDC were better than glutaraldehyde.

Keywords: Cross-linking agents, EDC, glutaraldehyde, immobilization, L-asparaginase, silica nanoparticles.

Graphical Abstract