Non Inflammatory Boronate Based Glucose-Responsive Insulin Delivery Systems

作者：Dasgupta Indrani^*; Tanifum Eric A; Srivastava Mayank; Phatak Sharangdhar S; Cavasotto Claudio N; Analoui Mostafa; Annapragada Ananth

来源：PLos One, 2012, 7(1): e29585.

DOI：10.1371/journal.pone.0029585

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.

• 出版日期2012-1-17