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

Autor(es)

Apolinario, Alexsandra Conceicao ; Ferraro, Rafael Bertelli ; de Oliveira, Camila Areias ; Pessoa, Adalberto, Jr. ; Rangel-Yagui, Carlota de Oliveira

• Tipo de documento: Artigo Científico
• Fonte: AAPS PHARMSCITECH; v. 20, n. 6, p. 12-pg., 2019-08-01.

Resumo

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)

• Processo FAPESP: 14/10456-4 - Desenvolvimento e caracterização de Polimerossomos de poli (óxido de Etileno-beta-ácido láctico) (PEG-PLA) para veiculação de L-asparaginase recombinante
• Beneficiário: Alexsandra Conceição Apolinário
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/03887-4 - Desenvolvimento e avaliação da segurança pré-clínica de nanoestruturas poliméricas para encapsulação da fotoliase
• Beneficiário: Camila Areias de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/08617-7 - Produção de L-asparaginase extracelular: da bioprospecção à engenharia de um biofármaco antileucêmico
• Beneficiário: Adalberto Pessoa Junior
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/03811-0 - Encapsulação da L-asparaginase em polimerossomos por variação de pH e eletroporação
• Beneficiário: Alexsandra Conceição Apolinário
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado