Boronic Acid Based Microparticulate Insulin Delivery System

DASGUPTA, I,; SRIVASTAVA, M.; TANIFUM, E.A.; PHATAK, SHARANGDHAR S.; CAVASOTTO, CLAUDIO N.; ANNAPRAGADA, ANANTH

Austin, TX

Simposio; Annual Meeting of the Biomedical Engineering Society; 2010

Our group previously demonstrated a self-regulating insulin delivery system that releases insulin in response to endogenous glucose concentrations, controlling blood glucose levels for long periods 1.The preparation consisted of an agglomerate of glucose cleavable nanoparticles, (Agglomerated vesicle technology:AVT). The compound originally used for cross-linking the nanoparticles was the lectin ConcanavalinA, known to be both toxic and highly inflammatory. 2.In this study we sought to identify a cross-linker to replace ConA. Boronic acids are known to bind diols, and can potentially replace ConA in this application 3. We therefore screened a large number of boronic acid derivatives for their toxicity and inflammatory properties and identified lead compounds that can safely be used in vivo. The sugar binding affinities of the leads were compared with those of ConA.Lead compounds selected from the screening efforts (phenylboronic acid derivatives) were conjugated to nanoparticles and used as a replacement for ConA to form boronic acid linked AVTs. The in vitro insulin release profiles of the boronic acid-AVT were confirmed to be similar to that of the ConA-AVT. Development of a modulated, long acting insulin delivery system,minimizing the number of daily injections and avoiding episodes of hypoglycemia, will significantly improve the quality of type 1 diabetes care and reduce the probability of serious side effects associated with inadequate control of blood glucose levels.