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Development of porous polymersomes with amphotericin B channels for L-asparaginase encapsulation

Grant number: 17/05272-0
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): June 01, 2017
Effective date (End): May 31, 2018
Field of knowledge:Engineering - Chemical Engineering
Principal Investigator:Carlota de Oliveira Rangel Yagui
Grantee:Cecilia Zorzi Bueno
Supervisor abroad: Giuseppe Battaglia
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : University College London (UCL), England  
Associated to the scholarship:16/16221-4 - Development of polymersomes permeable to L-asparagine for encapsulation of L-asparaginase, BP.PD

Abstract

The present proposal is included in the context of project Fapesp 2016/16221-4, in which a research internship abroad was planned at University College London (UCL) under supervision of Prof. Giuseppe Battaglia. The focus of this project is the development of novel nanocarriers containing the enzyme L-asparaginase (ASNase). This enzyme has been used to treat acute lymphoblastic leukaemia and non-Hodking's lymphoma since it catalyses the hydrolysis of L-asparagine (Asn), an essential amino acid to these tumour cells. However, ASNase is associated with various side effects and may be inactivated by circulating antibodies. The improvement of ASNase stability, bioavailability and biocompatibility may be achieved by its encapsulation in polymeric nanovesicles, or polymersomes. Specifically, this research project aims at the development of porous polymersomes, which will be permeable to Asn and maintain the enzyme entrapped and protected against antibodies and serum proteases. To create pores in the polymersome membranes, we will incorporate the antifungal agent amphotericin B (AmB), known to form channels permeable to ions and small molecules in cellular membranes, mainly in the presence of ergosterol. Different formulations containing the copolymer PMPC-PDPA (poly(2-methacryloyloxyethyl phosphorylcholine)-b-poly(2-diisopropylamino ethyl methacrylate), AmB and ergosterol in different proportions will be tested. The obtained polymersomes will be characterized regarding size, morphology, encapsulation efficiency and rate of Asn depletion. It is important to highlight that the original project has undergone some minor modifications to enable better chances of obtaining porous polymersomes, namely, the use of different phospholipids (POPC and DPPC) was replaced by the use of AmB and ergosterol. Finally, we would like to add that the collaboration of Prof. Battaglia, one of the leading researchers in the area of polymersomes, will be essential for the success of the project and for the development of this field in Brazil. (AU)