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

Author(s)

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

• Document type: Journal article
• Source: AAPS PHARMSCITECH; v. 20, n. 6, p. 12-pg., 2019-08-01.

Abstract

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: 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
• 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: 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: 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