Compartmentalization of therapeutic proteins into semi-crystalline PEG-PCL polymersomes

Autor(es)

Pachioni-Vasconcelos, Juliana de Almeida ^[1] ; Apolinario, Alexsandra Conceicao ^[1] ; Lopes, Andre Moreni ^[2] ; Pessoa, Jr., Adalberto ^[1] ; Barbosa, Leandro Ramos Souza ^[3] ; Rangel-Yagui, Carlota de Oliveira ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Biochem & Pharmaceut Technol, Sao Paulo - Brazil

^[2] Univ Estadual Campinas, Fac Pharmaceut Sci, Campinas - Brazil

^[3] Univ Sao Paulo, Inst Phys, Dept Gen Phys, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SOFT MATERIALS; v. 19, n. 2, p. 222-230, APR 3 2021.
• Citações Web of Science: 2

Resumo

Polymersomes are self-assembled nanostructures with high loading capacity, possibility to deliver hydrophilic as well as hydrophobic drugs and stealth characteristic resulting in low immunogenicity. These vesicles can be used to deliver enzyme drugs such as L-asparaginase (ASNase), a first line drug for acute lymphoblastic leukemia treatment. Here, polymersomes based on three semi-crystalline copolymers of poly(ethylene glycol)-b-poly(epsilon-caprolactone), namely PEG(45)PCL(44), PEG(114)PCL(98), and PEG(114)PCL(114), were investigated for the encapsulation of ASNase, as well as of bovine serum albumin (BSA) as a model protein. Critical aggregation concentration (CAC) of the copolymers was determined by fluorescence spectroscopy and the values varied from 0.6 to 1.26 mg/L. Using film hydration, polymersomes of 200-400 nm and narrow size distribution (polydispersity index values of 0.2-0.3) were obtained when centrifugation was used as a post-film technique. The encapsulation efficiency (EE %) was determined either after centrifugation of the suspension, followed by the proteins measurement in the supernatant or after Size Exclusion Chromatography (SEC) purification, in which the quantification was performed in the eluted fractions corresponding to the free protein. Higher encapsulation efficiency values were obtained after centrifugation (EE% approximate to 20%) in comparison to the measurements after SEC (EE% approximate to 1-5%), indicating that the protein could be partially entrapped in the polymeric network when centrifugation is used as separation method. Nonetheless, this system could provide an initial effect of the free ASNase followed by a long-term effect based on the encapsulated enzyme, leading to decreased dose administration. (AU)

• 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: 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: 17/10789-1 - Terapia combinatória utilizando polimerossomos decorados com transferrina e incorporados em hidrogéis de quitosana como smart drug delivery systems para células tumorais de melanoma
• Beneficiário: André Moreni Lopes
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores