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Encapsulation of L-asparaginase in polymersomes by pH-switch method and electroporation

Grant number: 17/03811-0
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): April 01, 2017
Effective date (End): September 30, 2017
Field of knowledge:Engineering - Chemical Engineering - Chemical Technology
Principal Investigator:Carlota de Oliveira Rangel Yagui
Grantee:Alexsandra Conceição Apolinário
Supervisor: Giuseppe Battaglia
Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: University College London (UCL), England  
Associated to the scholarship:14/10456-4 - Development and characterization of poly(ethylene glycol) methyl ether-Block-Poly (D,L-Lactide) (PEG-PLA) Polymersomes for the release of recombinant L-asparaginase, BP.DR


Nanostructures for L-Asparaginase (ASNase) drug delivery could overcome its fast plasma clearance by encapsulating this enzyme in an internal compartment. Additionally, this strategy allows either the stealth and/or controlled release of the protein. Among different nanotechnological approaches for proteins delivery, polymersomes appear to be very promising. Polymersomes are formed through self-assembly of block copolymers in aqueous solution and combine the vesicular structure of liposomes with the toughness of polymeric nanocarriers. Although our group have already prepared polymersomes of poly(ethylene glycol)-poly(lactic acid) with low polydispersity index employing the film hydration method, we have achieved low yields in vesicles and low encapsulation efficiency for ASNase. Therefore, we are applying for a BEPE fellowship to develop polymersomes in adequate concentrations, low polydispersity and higher encapsulation efficiency for ASNase in collaboration with Prof. Giuseppe Battaglia, one of the pioneers in polymersomes research for drug delivery. We will use the pH switch method and electroporation to form polymersomes of the pH responsible copolymer poly(ethylene glycol)-poly(2-(diisopropyl amine)ethyl methacrylate (PEG-PDPA), an amphiphilic copolymer widely employed by Battaglia Research Group. Dynamic light scattering and transmission electron microscopy will be used to characterize the polymersomes and encapsulation efficiency will be determined by size exclusion chromatography. Additionally, we highlight the opportunity for the candidate's personal and professional training since Prof. Battaglia is among the top researchers in the world working with polymersomes.

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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, . (17/03811-0, 16/16221-4, 17/05272-0, 13/08617-7)
APOLINARIO, ALEXSANDRA CONCEICAO; FERRARO, RAFAEL BERTELLI; DE OLIVEIRA, CAMILA AREIAS; PESSOA, JR., ADALBERTO; RANGEL-YAGUI, CARLOTA DE OLIVEIRA. Quality-by-Design Approach for Biological API Encapsulation into Polymersomes Using ``Off-the-Shelf{''} Materials: a Study on L-Asparaginase. AAPS PHARMSCITECH, v. 20, n. 6, . (17/03811-0, 13/08617-7, 16/03887-4, 14/10456-4)

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