School of Biomedical Informatics, The University of Texas Health Sciences Center at Houston, Houston, Texas, United States of America.
PLoS One. 2012;7(1):e29585. doi: 10.1371/journal.pone.0029585. Epub 2012 Jan 17.
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.
硼酸，已知能与二醇结合，被筛选出来作为非炎症交联剂，用于制备葡萄糖敏感和胰岛素释放的脂质体聚集物（聚集囊泡技术-AVT）。这样做是为了选择一种合适的替代物来替代以前使用的交联剂——伴刀豆球蛋白 A（ConA），这种凝集素在体内既有毒性又有炎症作用。从涉及炎症潜力、细胞毒性和葡萄糖结合测试的筛选中选择出先导化合物，然后将其与包封胰岛素的纳米颗粒连接，并通过糖硼酸酯键聚集形成 AVTs。在体外，这些颗粒在暴露于生理相关浓度的葡萄糖（10 毫摩尔/L-40 毫摩尔/L）时表现出胰岛素的触发释放。聚集物也被证明能够对几个小时内多个葡萄糖水平的峰值做出反应，以葡萄糖触发浓度定义的速率释放胰岛素。
