Title:Enhancement in Biological Activity of L-Asparginase by its Conjugation on Silica Nanoparticles
Volume: 12
Issue: 1
Author(s): Dorsa Golestaneh and Jaleh Varshosaz*
Affiliation:
- Department of Pharmaceutics, Faculty of Pharmacy and Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, Isfahan,Iran
Keywords:
Cross-linking agents, EDC, glutaraldehyde, immobilization, L-asparaginase, silica nanoparticles.
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.
