access icon free Enhanced stability of L-asparaginase by its bioconjugation to poly(styrene-co-maleic acid) and Ecoflex nanoparticles

© The Institution of Engineering and Technology
Received 08/07/2017, Accepted 13/12/2017, Revised 14/11/2017, Published 19/12/2017

Acute lymphoblastic leukemia (ALL) is the white blood cell cancer in children. L-asparaginase (L-ASNase) is one of the first drugs used in ALL treatment. Anti-tumor activity of L-ASNase is not specific and indicates limited stability in different biological environments, in addition to its quick clearance from blood. The purpose of the present study was to achieve a new L-ASNase polymer bioconjugate to improve pharmacokinetic, increase half-life and stability of the enzyme. The conjugations were achieved by the cross-linking agent of 1-ethyl-3-(3- dimethylaminopropyl) carbodiimide (EDC) which activates the carboxylic acid groups of polymeric nanoparticles to create amide bond. EDC conjugated the L-ASNase to two biodegradable polymers including; Ecoflex® and poly (styrene-co-maleic acid) (PSMA) nanoparticles. To achieve optimal L-ASNase nanoparticles the amounts of each polymer and the crosslinker were optimized and the nanoparticles were characterized according to their particle size, zeta potential and percent of conjugation of the enzyme. The results showed that conjugated enzyme had more stability against pH changes and proteolysis. It had lower Km value (indicating more affinity to the substrate) and greater half-life in plasma and phosphate buffered saline, in comparison to native enzyme. Generally, the conjugated enzyme to PSMA nanoparticles showed greater results than Ecoflex® nanoparticles.

Inspec keywords: biochemistry; nanomedicine; blood; particle size; pH; biomedical materials; molecular configurations; enzymes; conducting polymers; nanoparticles; electrokinetic effects; polymer blends; molecular biophysics; cancer; biodegradable materials; bonds (chemical)

Other keywords: amide bond; Ecoflex nanoparticles; conjugated enzyme; children; poly(styrene-co-maleic acid); polymeric nanoparticles; ALL treatment; 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide; proteolysis; PSMA nanoparticles; pharmacokinetic; acute lymphoblastic leukaemia; crosslinking agent; pH changes; EDC conjugation; antitumour activity; enzyme; enhanced stability; zeta potential; drugs; particle size; biodegradable polymers; L-ASNase polymer bioconjugate; L-asparaginase; white blood cell cancer; biological environments; native enzyme; bioconjugation; carboxylic acid groups; optimal L-ASNase nanoparticles

Subjects: Biomolecular structure, configuration, conformation, and active sites; Biomedical materials; Other methods of nanofabrication; Physical chemistry of biomolecular solutions and condensed states; Biomolecular interactions, charge transfer complexes; Molecular bond strengths, dissociation energies, hydrogen bonding; Electrochemistry and electrophoresis; Macromolecular configuration (bonds, dimensions); Structure of solid clusters, nanoparticles, nanotubes and nanostructured materials; Nanotechnology applications in biomedicine

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