L-Asparaginase delivery systems targeted to minimize its side-effects
Talluri V.P. Mutaliyeva B. Sharipova A. Ulaganathan V. Lanka S.S. Aidarova S. Suigenbayeva A. Tleuova A.
June 2023Elsevier B.V.
Advances in Colloid and Interface Science
2023#316
L-asparaginase (L-ASP) is one of the key enzymes used in therapeutic applications, particularly to treat Acute Lymphocytic Leukemia (ALL). L-asparagine is a non-essential amino acid, which means that it can be synthesized by the body and is not required to be obtained through the diet. The synthesis of L-asparagine occurs primarily in the liver, but it also takes place in other tissues throughout the body. In contrast, leukemic cells cannot synthesize L-asparagine due the absence of L-asparagine synthetase and should obtain it from circulating sources for protein synthesis and cell division processes to ensure their vital functions. L-ASP catalyzes the deamination process of L-asparagine amino-acid into aspartic acid and ammonia, depriving leukemic cells of asparagine. This leads to decreased protein synthesis and cell division in tumor cells. However, using L-ASP has side effects, such as hypersensitivity or allergic reaction, antigenicity, short half-life, temporary blood clearance, and toxicity. L-ASP immobilization can minimize the side effects of L-ASP by stopping the immune system from attacking non-human enzymes and improving the enzymes performance. The first strategy includes modification of enzyme structure, such as covalent binding (conjugation), adsorption to the support material and cross-linking of the enzyme. The chemical modification of residues, often nonspecific, changes the enzymes hydrophobicity and surface charge, lowering the enzymes activity. Also, the first strategy exposes the enzymes surface to the environment. This eliminates its performance and does not allow targeted delivery of the enzyme. The second strategy is based on the entrapment of the enzyme inside the protecting structure or encapsulation. This strategy offers the same benefits as the first. Still, it also enables reducing toxicity, prolonging in vivo half-life, enhancing stability and activity, enables a targeted delivery and controlled release of the enzyme. Compared to the first strategy, encapsulation does not modify the chemical structure of the enzyme since L-ASP is only effective against leukemia in its native tetrameric form. This review aims to present state of the art in L-ASP formulations developed for reducing the side effects of L-ASP, focusing on describing improvements in their safety. The primary focus in the field remains to be improving the overall performance of the L-ASP formulations. Almost all encapsulation systems allow reducing immune response due to screening the enzyme from antibodies and prolonging its half-life. However, the enzymes activity and stability depend on the encapsulation system type. Therefore, the selection of the right encapsulation system is crucial in therapy due to its effect on the performance parameters of the L-ASP. Biodegradable and biocompatible materials, such as chitosan, alginate and liposomes, mainly attract the researchers interest in enzyme encapsulation. The research trends are also moving towards developing formulations with targeted delivery and increased selectivity.
Delivery system , Encapsulation , L-asparaginase , Microencapsulation , Nanoencapsulation , Protein drug delivery
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National University of Singapore, 117546, Singapore
M. Auezov South Kazakhstan University, Shymkent, 160012, Kazakhstan
Satbayev University, Almaty, 050013, Kazakhstan
Institute of Agrophysics, Polish Academy of Sciences, Lublin, 20-290, Poland
Gandhi Institute of Technology and Management (GITAM) University, Andhra Pradesh, Visakhapatnam, 530045, India
Kazakh-British Technical University, Almaty, 050005, Kazakhstan
National University of Singapore
M. Auezov South Kazakhstan University
Satbayev University
Institute of Agrophysics
Gandhi Institute of Technology and Management (GITAM) University
Kazakh-British Technical University
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