title: Controlled release of insulin in blood from strontium-substituted carbonate apatite complexes.
abstract: 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.
authors.forename: Aiman
authors.initials: A
authors.lastname: Ahmad
authors.forename: Iekhsan
authors.initials: I
authors.lastname: Othman
authors.forename: Anuar Zaini
authors.initials: AZ
authors.lastname: Md Zain
authors.affiliation: Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia. md.ezharul.hoque@monash.edu.
authors.forename: Ezharul Hoque
authors.initials: EH
authors.lastname: Chowdhury
mesh_terms: D001031:Apatites / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000737:chemistry*; D065546:Drug Liberation; D006801:Humans; D007328:Insulin / Q000097:blood*; D053758:Nanoparticles / Q000737:chemistry; D013324:Strontium / Q000737:chemistry*
chemical_list: D001031:Apatites; D003692:Delayed-Action Preparations; D007328:Insulin; C030782:carboapatite; D013324:Strontium