Controlled Release of Insulin in Blood from Strontium-Substituted Carbonate Apatite Complexes
Anuar Zaini Md Zain,
Ezharul Hoque Chowdhury.
Diabetes mellitus is a chronic disease accompanied by a multitude of problems worldwide
with subcutaneously administered insulin being the most common therapy currently. Controlledrelease
insulin is assumed to be of high importance for long-term glycaemic control by reducing the
number of daily injections. Long-acting insulin also mimics the basal insulin levels in normal individuals
that may be lacking in diabetic patients. Nanoparticles of carbonate apatite as established for
efficient intracellular transport of DNA and siRNA have the potential to be used for sustained release
of insulin as responsive nano-carriers. The flexibility in the synthesis of the particles over a wide range
of pHs with eventual adjustment of pH-dependent particle dissolution and the manageable variability
of particle-integrity by incorporating selective ions into the apatite structure are the promising features that could help in
the development of sustained release formulations for insulin. In particular strontium-incorporated carbonate apatite particles
were formulated and compared with those of unsubstituted apatite in the context of insulin binding and subsequent release
kinetics in DMEM, simulated buffer and finally human blood over a period of 20 hours. Clearly, the former demonstated
to have a stronger electrostatic affinity towards the acidic insulin molecules and facilitate to some extent sustained
release of insulin by preventing the initial burst effect at physiological pH in comparison with the latter. Thus, our findings
suggest that optimization of the carbonate apatite particle composition and structure would serve to design an ideal
insulin nano-carrier with a controlled release profile.
Keywords: Blood, controlled dissolution, carbonate apatite particle, insulin, solubility, sustained release.
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