Development of polymersomes permeable to L-asparagine for encapsulation of L-asparaginase

• Grant number: 16/16221-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): October 01, 2016
• Effective date (End): September 30, 2019
• Field of knowledge: Engineering - Chemical Engineering - Chemical Technology
• Principal Investigator: Carlota de Oliveira Rangel Yagui
• Grantee: Cecilia Zorzi Bueno
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/08617-7 - Production of extracellular L-asparaginase: from bioprospecting to the engineering of an antileukemic biopharmaceutical, AP.TEM
• Associated scholarship(s): 17/05272-0 - Development of porous polymersomes with amphotericin B channels for L-asparaginase encapsulation, BE.EP.PD

Abstract

This proposal is a sub-project of the thematic project Fapesp No 2013/086 17-7 entitled "Production of extracellular L-asparaginase: from bioprospecting to the engineering of an antileukemic biopharmaceutical" headed by Prof. Adalberto Pessoa Jr., and is included in the workplan "Nanotechnological development of L- asparaginase for pharmaceutical formulation", under the responsibility of Prof. Carlota Rangel Yagui. This proposal also counts on the collaboration of Prof. Giuseppe Battaglia, from University College London, so that a research stage in that institution is expected. The focus of this project is the treatment of Acute Lymphoblastic Leukaemia, in which the enzyme L-asparaginase is an essential component. This enzyme has antineoplastic activity by catalysing the hydrolysis reaction of the amino acid L-asparagine, which is essential to tumour cells. To improve L-asparaginase stability, bioavailability, toxicity and allergenicity, the enzyme will be encapsulated in polymersomes, which are nanovesicles made of amphiphilic copolymers. This proposal involves the development of polymersomes permeable to L-asparagine, so that the enzyme would remain entrapped and protected against a hostile environment during treatment. To accomplish this, the copolymer PEG-PCL will be mixed to different phospholipids (DPPC and POPC) in different mass proportions, forming hybrid vesicles. Polymersomes containing or not encapsulated L-asparaginase will be characterized regarding morphology and physicochemical parameters. Finally, encapsulation efficiency and the rate of L-asparagine depletion will be evaluated. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BUENO, CECILIA Z.; APOLINARIO, ALEXSANDRA C.; DURO-CASTANO, AROA; POMA, ALESSANDRO; PESSOA, JR., ADALBERTO; RANGEL-YAGUI, CARLOTA O.; BATTAGLIA, GIUSEPPE. L-Asparaginase Encapsulation into Asymmetric Permeable Polymersomes. ACS MACRO LETTERS, v. 9, n. 10, p. 1471-1477, OCT 20 2020. (17/03811-0, 16/16221-4, 17/05272-0, 13/08617-7)