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 recovery decreased aggregation and led to a narrower nanoscale particle-size distribution. Insulin encapsulation efficiency was 99.3%±0.5%, attributed to the strong pH-stabilizing electrostatic effect between insulin and nanoparticle matrix polymers. Interactions between these polymers and insulin were predicted using molecular modeling studies through quantum mechanics calculations that allowed for prediction of the interaction model. In vitro release studies indicated well-preserved integrity of nanoparticles in simulated gastric fluid. Circular dichroism spectroscopy proved conformational stability of insulin and Fourier transform infrared spectroscopy technique showed rearrangements of insulin structure during processing. Moreover, in vivo biological activity in diabetic rats revealed no statistical difference when compared to nonencapsulated insulin, demonstrating retention of insulin activity. Our results demonstrate that alginate–dextran sulfate-based nanoparticles efficiently stabilize the loaded protein structure, presenting good physical properties for oral delivery of insulin. Keywords: biopolymers, insulin secondary structure, microparticle, molecular modeling, nanoencapsulation processing, oral deliver

Análise das publicações nacionais sobre educação à distância na enfermagem Análisis de las publicaciones nacionales acerca de la educación a la distancia en enfermería Analysis of national publications about distance education in nursing

O objetivo é analisar as publicações que trabalham a Educação à Distância na Enfermagem nas principais bases de dados de 2005 a 2009. Estudo de revisão de literatura sistemática realizada nas bases de dados da Biblioteca Virtual da Saúde (Lilacs, Scielo e Bdenf), no período de 19/02/09 à 24/04/09 em 20 referências analisadas. Destacam-se como tônica nas discussões: o desenvolvimento de cursos de capacitação para profissionais de enfermagem bem como em disciplinas nos cursos de graduação via Educação à Distância. Há uma evolução da Educação à Distância na Enfermagem com possibilidades de ensino no ambiente virtual de aprendizagem são inesgotáveis e levam em consideração alguns condicionantes relevantes para interatividade como a disponibilidade de cursos de capacitação e disciplinas nos cursos de graduação.<br>El objetivo es examinar las publicaciones que trabajan la educación a distancia en enfermería en las principales bases de datos de 2005 a 2009. Estudio de revisión de literatura realizada en las bases de datos de la Biblioteca Virtual de Salud (Lilacs, Scielo y Bdenf) en el período comprendido entre 19/02/09 al 24/04/09 en 20 referencias. Es tónico en las discusiones: el desarrollo de cursos de capacitación para profisionales de enfermería, cursos en programas de postgrado a través de la educación a distancia. Hay una evolución en la educación a distancia de enfermería con posibilidades de enseñanza en el ambiente virtual de aprendizaje es inagotable y tenen algunas condiciones pertinentes para interactividad como la disponibilidad de cursos de formación y disciplinas de graduación.<br>The objective is to examine the publications working in the Distance Education in nursing in the databases from 2005 to 2009. Study of literature review conducted in the databases of the Virtual Health Library (Lilacs, Scielo and Bdenf) in the period from 19/02/09 to 24/04/09 in 20 selected references were reviewed. It is tonic in the discussions: the development of training courses for nurses and midwives as well as courses in graduate programs via Distance Education. There is an evolution of Distance Education in nursing with possibilities of teaching in virtual environment for learning is everlasting and take into account some constraints relevant to interactivity as the availability of training courses and disciplines in undergraduate courses