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TitleAlbumin/asparaginase capsules prepared by ultrasound to retain ammonia
Author(s)Tinoco, Ana Catarina Malheiro
Ribeiro, Artur J.
Oliveira, César João Santos
Parpot, Pier
Gomes, Andreia
Cavaco-Paulo, Artur
KeywordsAcute lymphoblastic leukemia
Ammonia retention
Issue dateNov-2016
JournalApplied Microbiology and Biotechnology
CitationTinoco, A.; Ribeiro, Artur; Oliveira, César; Parpot, Pier; Gomes, Andreia; Cavaco-Paulo, Artur, Albumin/asparaginase capsules prepared by ultrasound to retain ammonia. Applied Microbiology and Biotechnology, 100(22), 9499-9508, 2016
Abstract(s)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.
Description"Published online: 17 June 2016"
Publisher version
AccessOpen access
Appears in Collections:CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series

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