Albumin/asparaginase capsules prepared by ultrasound to retain ammonia.
Asparaginase reduces the levels of asparagine in blood, which is an essential amino acid for the proliferation of lymphoblastic malign cells. Asparaginase converts asparagine into aspartic acid and ammonia. The accumulation of ammonia in the bloodstream leads to hyperammonemia, described as one of the most significant side effects of asparaginase therapy. Therefore, there is a need for asparaginase formulations with the potential to reduce hyperammonemia. We incorporated 2 % of therapeutic enzyme in albumin-based capsules. The presence of asparaginase in the interface of bovine serum albumin (BSA) capsules showed the ability to hydrolyze the asparagine and retain the forming ammonia at the surface of the capsules. The incorporation of Poloxamer 407 in the capsule formulation further increased the ratio aspartic acid/ammonia from 1.92 to 2.46 (and 1.10 from the free enzyme), decreasing the levels of free ammonia. This capacity to retain ammonia can be due to electrostatic interactions and retention of ammonia at the surface of the capsules. The developed BSA/asparaginase capsules did not cause significant cytotoxic effect on mouse leukemic macrophage cell line RAW 264.7. The new BSA/asparaginase capsules could potentially be used in the treatment of acute lymphoblastic leukemia preventing hyperammonemia associated with acute lymphoblastic leukemia (ALL) treatment with asparaginase.
CEB-Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.
Ana
A
Tinoco
CEB-Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.|CBMA-Centre of Molecular and Environmental Biology, University of Minho, 4710-057, Braga, Portugal.
Artur
A
Ribeiro
Centre of Chemistry, Department of Chemistry, University of Minho, 4710-057, Braga, Portugal.
César
C
Oliveira
Centre of Chemistry, Department of Chemistry, University of Minho, 4710-057, Braga, Portugal.
Pier
P
Parpot
CBMA-Centre of Molecular and Environmental Biology, University of Minho, 4710-057, Braga, Portugal.
Andreia
A
Gomes
CEB-Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal. artur@deb.uminho.pt.
Artur
http://orcid.org/0000-0001-7204-2064
A
Cavaco-Paulo
D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000633:toxicity; D001215:Asparaginase / Q000378:metabolism* / Q000633:toxicity; D002214:Capsules / Q000378:metabolism*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D000067996:RAW 264.7 Cells; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D014463:Ultrasonography
D000970:Antineoplastic Agents; D002214:Capsules; D004337:Drug Carriers; D012710:Serum Albumin, Bovine; D000641:Ammonia; D001215:Asparaginase
Acute lymphoblastic leukemia; Ammonia retention; Asparaginase; Capsules; Ultrasound