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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Quality-by-Design Approach for Biological API Encapsulation into Polymersomes Using ``Off-the-Shelf{''} Materials: a Study on L-Asparaginase

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Apolinario, Alexsandra Conceicao [1] ; Ferraro, Rafael Bertelli [1] ; de Oliveira, Camila Areias [1] ; Pessoa, Jr., Adalberto [1] ; Rangel-Yagui, Carlota de Oliveira [1]
Total Authors: 5
[1] Univ Sao Paulo, Dept Biochem & Pharmaceut Technol, Sch Pharmaceut Sci, Ave Prof Lineu Prestes 580-Bl 16, BR-05508000 Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: AAPS PHARMSCITECH; v. 20, n. 6 AUG 2019.
Web of Science Citations: 0

Polymersomes are versatile nanostructures for protein delivery with hydrophilic core suitable for large biomolecule encapsulation and protective stable corona. Nonetheless, pharmaceutical products based on polymersomes are not available in the market, yet. Here, using commercially available copolymers, we investigated the encapsulation of the active pharmaceutical ingredient (API) L-asparaginase, an enzyme used to treat acute lymphoblastic leukemia, in polymersomes through a quality-by-design (QbD) approach. This allows for streamlining of processes required for improved bioavailability and pharmaceutical activity. Polymersomes were prepared by bottom-up (temperature switch) and top-down (film hydration) methods employing the diblock copolymers poly(ethylene oxide)-poly(lactic acid) (PEG(45)-PLA(69), PEG(114)-PLA(153), and PEG(114)-PLA(180)) and the triblock Pluronic((R)) L-121 (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), PEG(5)-PPO68-PEG(5)). Quality Target Product Profile (QTPP), Critical Quality Attributes (CQAs), Critical Process Parameters (CPPs), and the risk assessment were discussed for the early phase of polymersome development. An Ishikawa diagram was elaborated focusing on analytical methods, raw materials, and processes for polymersome preparation and L-asparaginase encapsulation. PEG-PLA resulted in diluted polymersomes systems. Nonetheless, a much higher yield of Pluronic((R)) L-121 polymersomes of 200nm were produced by temperature switch, reaching 5% encapsulation efficiency. Based on these results, a risk estimation matrix was created for an initial risk assessment, which can help in the future development of other polymersome systems with biological APIs nanoencapsulated. (AU)

FAPESP's process: 17/03811-0 - Encapsulation of L-asparaginase in polymersomes by pH-switch method and electroporation
Grantee:Alexsandra Conceição Apolinário
Support Opportunities: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 13/08617-7 - Production of extracellular L-asparaginase: from bioprospecting to the engineering of an antileukemic biopharmaceutical
Grantee:Adalberto Pessoa Junior
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 16/03887-4 - Development and evaluation of pre-clinical safety of polymeric nanostructures for encapsulation of photolyase
Grantee:Camila Areias de Oliveira
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 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
Grantee:Alexsandra Conceição Apolinário
Support Opportunities: Scholarships in Brazil - Doctorate