BSA/ASN/Pol407 nanoparticles for acute lymphoblastic leukemia treatment

Abstract

During the treatment of acute lymphoblastic leukemia (ALL) with asparaginase (ASN) there is an accumulation of ammonia in the body as result of asparagine hydrolysis. This accumulation known as hyperammonemia is one of the main side-effects of this therapy. To avoid hyperammonemia is urgent to develop new strategies for ammonia retention. Herein is presented the immobilization of ASN into bovine serum albumin/poloxamer 407 (BSA/Pol407) nanoparticles. The ability of the developed nanoparticles to hydrolyze asparagine while retaining the forming ammonia is also explored. Different percentages of ASN were entrapped into BSA nanoparticles coated with Poloxamer 407 and were prepared by high-pressure homogenization. The nanoparticles were characterized regarding their physico-chemical properties, stability, capacity to retain ammonia and safety using zebrafish embryos as an in vivo model of toxicity. The BSA/ASN25%/Pol407 nanoparticles were selected as the best formulation to hydrolyze asparagine using the lowest nanoparticle concentration. These nanoparticles presented physical characteristics suitable for an intravenous application and were capable to retain the forming ammonia decreasing the negative effect of free ASN on zebrafish survival. These nanoparticles could potentially be used to prevent hyperammonemia during ALL treatment with ASN.