| Texto completo | |
| Autor(es): |
Javier, Muso-Cachumba Jorge
;
Grace, Ruiz-Lara
;
Sani, Alison Tatiana Madrid
;
Zanin, Maria Helena Ambrosio
;
Monteiro, Gisele
;
Lourenco, Felipe Rebello
;
Pessoa-Jr, Adalberto
;
Rangel-Yagui, Carlota
Número total de Autores: 8
|
| Tipo de documento: | Artigo Científico |
| Fonte: | JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY; v. 109, p. 13-pg., 2025-07-01. |
| Resumo | |
L-asparaginase (ASNase, EC 3.5.1.1) is an enzyme used as an antitumor agent in the treatment of Acute Lymphoid Leukemia (ALL); however, its use can lead to sensitization and immune response, as well as enzyme degradation by plasma proteases, decreasing the drug half-life and effectiveness. To improve these issues novel ASNase proteoforms were developed, as is the case of a recombinant glycosylated one expressed in Komagataella phaffii, as well as innovative formulations, such as enzyme encapsulation in polymersomes, that can increase the half-life and decrease adverse effects. Nonetheless, further investigation is needed to develop an adequate process for ASNase encapsulation aiming for better yields and an adequate drying method. In this work, we developed a dry formulation of glycosylated ASNase-loaded polymersomes of poloxamer 401 employing spraydrying and a Quality by Design approach. Fractional factorial and central rotational composite experimental designs were performed to obtain the final dry formulation. In a first step, the optimized values of sucrose (180 mM) as osmolyte and ASNase (1.5 mg/mL) resulted in an encapsulation efficiency (%EE) of 10 f 2 % and an asparaginolytic activity of 0.297 f 0.087 U/mL. In the next step and after optimization, 100 degrees C inlet temperature, 3 % maltodextrin DE20 as diluent, feed rate of 3.0 mL/min and atomization air flow of 750 LN/h were used to achieve a recovery yield of powder of 69 f 2 % after spray drying. Finally, the cytotoxicity against ALL tumor cell line was investigated using the MTT assay and the dry powder formulation of ASNase-loaded polymersomes presented the highest antitumor effect (IC50 = 0.00225 f 0.00009 U/mL), proving that the drying process did not impair the cytotoxic activity of the biopharmaceutical. Therefore, we developed a dry powder formulation of ASNase loaded polymersomes based on a promising mutant enzyme that corresponds to a novel potential alternative to treat ALL. The dry powder formulation of nano-in-microparticles might increase ASNase shelf-life stability, in vivo half-life, as well as decrease toxicity. (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: | 18/15104-0 - Ensaios pré-clínicos de proteoformas de asparaginase glicoproteicas ou resistentes a proteases séricas. |
| Beneficiário: | Gisele Monteiro |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |