Influence and effect of osmolytes in biopharmaceutical formulations

Autor(es)

Wlodarczyk, Samarina R. ^[1] ; Custodio, Debora ^[1] ; Pessoa Jr, Adalberto ; Monteiro, Gisele ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Biochem & Pharmaceut Technol, BR-05434070 Sao Paulo, SP - Brazil

^[2] Pessoa Jr, Jr., Adalberto, Univ Sao Paulo, Fac Pharmaceut Sci, Dept Biochem & Pharmaceut Technol, BR-05434070 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS; v. 131, p. 92-98, OCT 2018.
• Citações Web of Science: 5

Resumo

Osmolytes are small organic molecules accumulated by cells in response to environmental stresses. They are represented by amino acids, sugars, polyols, tertiary sulphonium and quaternary ammonium compounds. These molecules present a protective behaviour and favour the equilibrium of macromolecules towards the native form, preventing denaturation and promoting the folding of unfolded proteins. Protein formulations due to their biological character require greater care during the manufacturing process, shelf-life and administration of the drug, as variations in these factors may result in denaturation, inactivation and/or protein aggregation. These drawbacks can be surpassed using osmolytes as excipients in protein formulations as stabilisers, bulking agents and even buffers. A number of 133 biologics, including vaccines and immunoglobulins, approved by the U.S. Food and Drug Administration (FDA) between 1998 and 2017 were analysed in this work in order to identify the most used group of osmolyte molecules. A deep insight into their role in protein formulations was discussed and compared to data in the literature. The advantages and disadvantages of their use in specific formulations were also extensively discussed here. In conclusion, investigation into the role of osmolytes in each formulation is essential for understanding their effect and provides a background to be used when selecting the best osmolyte to fit a specific formulation without excluding the patient needs. (AU)

• Processo FAPESP: 15/24463-5 - Caracterização de L-asparaginase de Erwinia chrysanthemi melhorada por evolução sintética de proteínas e otimização das condições de produção
• Beneficiário: Débora Fernandes Custodio
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• 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: 13/24024-6 - Efeitos de interações proteína-meio aquoso em modificações estruturais da L- Asparaginase II de escherichia coli
• Beneficiário: Samarina Rodrigues Wlodarczyk
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/07749-2 - Engenharia de proteínas e comparação de sistemas microbianos de expressão do biofármaco L-asparaginase
• Beneficiário: Gisele Monteiro
• Modalidade de apoio: Auxílio à Pesquisa - Regular