Non inflammatory boronate based glucose-responsive insulin delivery systems

• Autores: Dasgupta, Indrani; Tanifum, Eric A.; Srivastava, Mayank; Phatak, Sharangdhar S.; Cavasotto, Claudio Norberto; Analoui, Mostafa; Annapragada, Ananth
• Año de publicación: 2012
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Drug delivery; Insulin delivery systems; Inflamation; Boronates
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Boronic acids, known to bind diols, were screened to identify non-inflammatory cross-linkers for the preparation of glucose sensitive and insulin releasing agglomerates of liposomes (Agglomerated Vesicle Technology-AVT). This was done in order to select a suitable replacement for the previously used cross-linker, ConcanavalinA (ConA), a lectin known to have both toxic and inflammatory effects in vivo. Lead-compounds were selected from screens that involved testing for inflammatory potential, cytotoxicity and glucose-binding. These were then conjugated to insulin-encapsulating nanoparticles and agglomerated via sugar-boronate ester linkages to form AVTs. In vitro, the particles demonstrated triggered release of insulin upon exposure to physiologically relevant concentrations of glucose (10 mmoles/L-40 mmoles/L). The agglomerates were also shown to be responsive to multiple spikes in glucose levels over several hours, releasing insulin at a rate defined by the concentration of the glucose trigger.
Fil: Dasgupta, Indrani. University of Texas; Estados Unidos
Fil: Tanifum, Eric A.. Baylor College of Medicine; Estados Unidos
Fil: Srivastava, Mayank. Baylor College of Medicine; Estados Unidos
Fil: Phatak, Sharangdhar S.. University of Texas; Estados Unidos
Fil: Cavasotto, Claudio Norberto. University of Texas; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Analoui, Mostafa. Cense Biosciences; Estados Unidos
Fil: Annapragada, Ananth. Baylor College of Medicine; Estados Unidos