Antileukemic biopharmaceuticals purification using supported ionic liquid materials based on silica

Abstract

Acute lymphoblastic leukemia (ALL) accounts with approximately 6500 new cases in the United States each year [1]. The first-line biopharmaceutical being used to treat ALL, Oncaspar, is based on L-asparaginase (LA), with annual sales of approximately USD $100 million [2]. Its purification accounts for up to 80% of total production cost [3], and therefore, it is crucial to find new strategies to purify LA in order to decrease its current cost and allow it routinely use by a widespread population. Supported ionic liquid materials based on silica (SILs) are already reported in the literature for the separation of natural compounds from vegetable biomass [4]. Although SILs represent a class of materials with high potential in the purification of proteins, this particular application has been scarcely considered [5]. In this work, the search for SILs able to establish (non-covalent) specific interactions with LA, allowing therefore its purification from the fermentation broth in which it is produced, was investigated. Commercial LA was used in a first set of experiments in order to understand the adsorption behavior of the enzyme on SILs. Experimental conditions, such as pH, contact time and SILs/LA ratio were evaluated and optimized in what concerns the LA yield. The results show that the ideal conditions for LA are a pH between 7-8 and contact time with SILs of 30 min. With the envisioned purification strategy, process costs, energy consumed, and waste generated, may be significantly decreased, which may lead to the LA cost decrease and wider application.