Development and characterization of poly(ethylene glycol) methyl ether-Block-Poly (D,L-Lactide) (PEG-PLA) Polymersomes for the release of recombinant L-asparaginase

• Grant number: 14/10456-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2014
• End date: July 31, 2018
• Field of knowledge: Engineering - Chemical Engineering - Chemical Technology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Carlota de Oliveira Rangel Yagui
• Grantee: Alexsandra Conceição Apolinário
• 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): 17/03811-0 - Encapsulation of L-asparaginase in polymersomes by pH-switch method and electroporation, BE.EP.DR

Abstract

This proposal is a subproject of the thematic project Fapesp No 2013/08617-7, entitled "Production of extracellular L-asparaginase: from bioprospecting to the engineering of an antileukemic biopharmaceutical" conceived by a multidisciplinary group of researchers 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. L-asparaginase is widely used as antineoplastic agent in the treatment of acute lymphoblastic leukemia. The enzyme catalyzes the hydrolysis of L-asparagine to aspartic acid and ammonia in the extracellular medium. Since the tumor cells require this amino acid for growth, it causes cell death. Some undesirable aspects related to the therapeutic use of L-asparaginase are short half-life and immunogenicity. Since L-asparaginase is a hydrophilic macromolecule of considerable size (~ 140 kDa), most of the nanotechnological alternatives available, such as polymeric nanoparticles and nanocapsules, are not good choices for its encapsulation. Polymersomes, on the other hand, are nanocarriers presenting hydrophilic core and a bilayer of amphiphilic copolymers. Therefore, they are able to encapsulate the enzyme, increasing its half-life and decreasing immunogenicity. In this context, this project refers to the development and characterization of polymersomes formed by biodegradable and biocompatible copolymers of poly (ethylene oxide- ²-lactic acid) (PEG-PLA), for the delivery and release of L- asparaginase. PEG-PLA copolymers of different molar mass will be employed. Initial studies will be conducted with pure commercial enzyme and, subsequently, the recombinant enzyme expressed in Pichia pastoris will be used. (AU)

Scientific publications

(9)

(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)

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, AUG 2019. (17/03811-0, 13/08617-7, 16/03887-4, 14/10456-4)

BRUMANO, LARISSA PEREIRA; SANTOS DA SILVA, FRANCISCO VITOR; COSTA-SILVA, TALES ALEXANDRE; APOLINARIO, ALEXSANDRA CONCEICAO; PICADO MADALENA SANTOS, JOAO HENRIQUE; KLEINGESINDS, EDUARDO KREBS; MONTEIRO, GISELE; RANGEL-YAGUI, CARLOTA DE OLIVEIRA; BENYAHIA, BRAHIM; PESSOA JUNIOR, ADALBERTO. Development of L-Asparaginase Biobetters: Current Research Status and Review of the Desirable Quality Profiles. FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, v. 6, JAN 10 2019. (14/10456-4, 15/07749-2, 18/03734-9, 13/08617-7, 17/21819-9)

PACHIONI-VASCONCELOS, JULIANA DE ALMEIDA; APOLINARIO, ALEXSANDRA CONCEICAO; LOPES, ANDRE MORENI; PESSOA, JR., ADALBERTO; BARBOSA, LEANDRO RAMOS SOUZA; RANGEL-YAGUI, CARLOTA DE OLIVEIRA. Compartmentalization of therapeutic proteins into semi-crystalline PEG-PCL polymersomes. SOFT MATERIALS, v. 19, n. 2, p. 222-230, APR 3 2021. (13/08617-7, 14/10456-4, 17/10789-1)

APOLINARIO, ALEXSANDRA CONCEICAO; MAGON, MONIKA S.; PESSOA JR, ADALBERTO; RANGEL-YAGUI, CARLOTA DE OLIVEIRA. Challenges for the Self-Assembly of Poly(Ethylene Glycol)-Poly(Lactic Acid) (PEG-PLA) into Polymersomes: Beyond the Theoretical Paradigms. NANOMATERIALS, v. 8, n. 6, JUN 2018. (13/08617-7, 14/10456-4)

PACHIONI-VASCONCELOS, JULIANA DE ALMEIDA; LOPES, ANDRE MORENI; APOLINARIO, ALEXSANDRA CONCEICAO; VALENZUELA-OSES, JOHANNA KARINA; RIBEIRO COSTA, JULIANA SOUZA; NASCIMENTO, LAURA DE OLIVEIRA; PESSOA, JR., ADALBERTO; SOUZA BARBOSA, LEANDRO RAMOS; RANGEL-YAGUI, CARLOTA DE OLIVEIRA. Nanostructures for protein drug delivery. BIOMATERIALS SCIENCE, v. 4, n. 2, p. 205-218, 2016. (14/01983-0, 13/16588-7, 13/08617-7, 14/10456-4)

ALEXSANDRA CONCEIÇÃO APOLINÁRIO; JULIANA DE ALMEIDA PACHIONI-VASCONCELOS; ADALBERTO PESSOA JR.; CARLOTA DE OLIVEIRA RANGEL-YAGUI. POLIMEROSSOMOS VERSUS LIPOSSOMOS: A EVOLUÇÃO DA “BALA MÁGICA”. Química Nova, v. 40, n. 7, p. 810-817, 2017-08-00. (14/10456-4, 13/08617-7)

MEDEIROS DE BRITO, ANNA EMMANUELA; PESSOA, JR., ADALBERTO; CONVERTI, ATTILIO; RANGEL-YAGUI, CARLOTA DE OLIVEIRA; DA SILVA, JOSE ALEXSANDRO; APOLINARIO, ALEXSANDRA CONCEICAO. Poly (lactic-co-glycolic acid) nanospheres allow for high L-asparaginase encapsulation yield and activity. Materials Science & Engineering C-Materials for Biological Applications, v. 98, p. 524-534, MAY 2019. (13/08617-7, 14/10456-4, 17/08123-5)

GUIMARAES, MARINA DE SOUZA; MUSO CACHUMBA, JORGE JAVIER; BUENO, CECILIA ZORZI; TORRES-OBREQUE, KARIN MARIANA; RUIZ LARA, GRACE VERONICA; MONTEIRO, GISELE; SOUZA BARBOSA, LEANDRO RAMOS; PESSOA JR, ADALBERTO; RANGEL-YAGUI, CARLOTA DE OLIVEIRA. Peg-Grafted Liposomes for L-Asparaginase Encapsulation. PHARMACEUTICS, v. 14, n. 9, p. 18-pg., 2022-09-01. (18/15104-0, 13/08617-7, 15/15822-1, 14/10456-4)

APOLINARIO, ALEXSANDRA CONCEICAO; FERRARO, RAFAEL BERTELLI; DE OLIVEIRA, CAMILA AREIAS; PESSOA, ADALBERTO, JR.; 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, p. 12-pg., 2019-08-01. (14/10456-4, 16/03887-4, 13/08617-7, 17/03811-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

APOLINÁRIO, Alexsandra Conceição. Development and characterization of polymersomes for the release of L-asparaginase. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.