Villanueva-Flores Francisca, Zárate-Romero Andrés, Torres Alfredo G, Huerta-Saquero Alejandro
Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Km. 107 Carretera Tijuana-Ensenada, Ensenada 22860, Mexico.
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77550, USA.
Pharmaceutics. 2021 Nov 19;13(11):1965. doi: 10.3390/pharmaceutics13111965.
Asparaginase (ASNase) is a widely applied chemotherapeutic drug that is used to treat Acute Lymphoblastic Leukemia (ALL); however, immune responses and silent inactivation of the drug often limit its bioavailability. Many strategies have been proposed to overcome these drawbacks, including the development of improved formulations (biobetters), but only two of them are currently on the market. Nano- and micro-encapsulation are some of the most promising and novel approaches to enhance in vivo performance of ASNase, preventing the direct contact of the enzyme with the environment, protecting it from protease degradation, increasing the enzymes catalytic half-life, and in some cases, reducing immunogenicity. This review summarizes the strategies, particularly for ASNase nano- and micro-encapsulation, and their main findings, constraints, and current gaps in the state-of-the-art knowledge. The pros and cons of the use of different nanocarriers are discussed with the idea to ultimately provide safer and more effective treatments for patients with ALL.
天冬酰胺酶（ASNase）是一种广泛应用的化疗药物，用于治疗急性淋巴细胞白血病（ALL）；然而，免疫反应和药物的沉默失活常常限制其生物利用度。已经提出了许多策略来克服这些缺点，包括开发改进的制剂（生物优化药），但目前只有两种上市。纳米和微囊化是提高ASNase体内性能最有前景和新颖的方法之一，可防止酶与环境直接接触，保护其免受蛋白酶降解，延长酶的催化半衰期，在某些情况下还可降低免疫原性。本综述总结了这些策略，特别是ASNase纳米和微囊化策略，以及它们的主要发现、限制和当前最新知识中的差距。讨论了使用不同纳米载体的优缺点，以期最终为ALL患者提供更安全、更有效的治疗方法。
