Probing insulin bioactivity in oral nanoparticles produced by ultrasonication-assisted emulsification/internal gelation

Marlene A Lopes,1,2,* Bárbara Abrahim-Vieira,3,* Claudia Oliveira,4,5 Pedro Fonte,6,7 Alessandra M T Souza,3 Tammy Lira,3 Joana A D Sequeira,1,2 Carlos R Rodrigues,3 Lúcio M Cabral,3 Bruno Sarmento,6–8 Raquel Seiça,9 Francisco Veiga,1,2 António J Ribeiro1,4,5 1Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; 2CNC – Center for Neuroscience and Cell Biology, Coimbra, Portugal; 3Department of Pharmaceutics, Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 4I3S, Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal; 5Group Genetics of Cognitive Dysfunction, IBMC – Instituto de Biologia Molecular e Celular, Porto, Portugal; 6REQUIMTE, Department of Chemical Sciences – Applied Chemistry Lab, Faculty of Pharmacy, University of Porto, Porto, Portugal; 7CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Gandra, Portugal; 8INEB – Instituto de Engenharia Biomédica, University of Porto, Porto, Portugal; 9IBILI – Institute of Biomedical Research in Light and Image, Faculty of Medicine, University of Coimbra, Coimbra, Portugal *These authors contributed equally to this work Abstract: Alginate–dextran sulfate-based particles obtained by emulsification/internal gelation technology can be considered suitable carriers for oral insulin delivery. A rational study focused on the emulsification and particle recovery steps was developed in order to reduce particles to the nanosize range while keeping insulin bioactivity. There was a decrease in size when ultrasonication was used during emulsification, which was more pronounced when a cosurfactant was added. Ultrasonication add-on after particle re