Non Inflammatory Boronate Based Glucose-Responsive Insulin Delivery Systems

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.

Poly(trimethylene carbonate)-based polymers engineered for biodegradable functional biomaterials

“…158 This polymer is promising as a glucose-responsive drug carrier for insulin delivery in the future. 194 Conjugation of fluorophores in the micelle core helps to monitor the stability of the micelle. A quinine-functionalized PTMC derivative in the form of the amphiphilic random copolymer indicated minimal fluorescence in water because of self-quenching of the quinine pendants in the micelle core, whereas the higher fluorescence emission was observed for the much shorter oligomer (dimer) and free quinine.…”

Polypeptide-participating complex nanoparticles with improved salt-tolerance as excellent candidates for intelligent insulin delivery

“…[3][4][5] Amongst these self-regulated insulin delivery systems, synthetic phenylboronic acid (PBA)-based polymeric materials with high stability have shown more promising applications than glucose oxidase (GOD) and lectin (Con A) based systems. [6][7][8] Until now, a variety of PBA-based glucose-responsive materials particularly in the form of nanoparticles including nanogels (microgels), [9][10][11] micelles, [12][13][14][15] vesicles, [16][17][18][19][20] and mesoporous silica nanoparticles 21,22 have been broadly explored and shown to exhibit effective glucose-responsiveness at physiological pH and reasonable glucose-sensitivity.…”

Possible Ways to Improve Postprandial Glucose Control in Type 1 Diabetes

“…One such approach uses boronate-based glucose sensing (that is attached to the insulin molecules) for continuous sensing. 115,116 Effective PPG control still requires multiple daily efforts that include, but are not limited to the following: proper and accurate assessment of carbohydrate intake (DAFNE trial), food composition, insulin dose adjustments based on physical activity, current glucose level (as measured by SMBG), or real-time CGM. 30 CGM data allow patients and healthcare providers real-time feedback to control PPG more effectively.…”