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