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

Grant number: 16/16221-4
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): October 01, 2016
Effective date (End): September 30, 2019
Field of knowledge:Engineering - Chemical Engineering
Principal Investigator:Carlota de Oliveira Rangel Yagui
Grantee:Cecilia Zorzi Bueno
Home 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)

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