non inflammatory boronate based glucose-responsive insulin delivery systems基于非炎性boronate glucose-responsive胰岛素输送系统.pdfVIP

Non Inflammatory Boronate Based Glucose-Responsive Insulin Delivery Systems 2 1 1 2 Indrani Dasgupta , Eric A. Tanifum , Mayank Srivastava , Sharangdhar S. Phatak , Claudio N. 2 3 1 Cavasotto , Mostafa Analoui , Ananth Annapragada * 1 Department of Pediatric Radiology, Texas Children9s Hospital and Baylor College of Medicine, Houston, Texas, United States of America, 2 School of Biomedical Informatics, The University of Texas Health Sciences Center at Houston, Houston, Texas, United States of America, 3 Cense Biosciences Inc., Manvel, Texas, United States of America Abstract 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. Citation: Dasgupta I, Tanifum EA, Srivastava M, Phatak SS, Cavasot