ALGINATE MICROSPHERES FOR MAGNETICALLY TRIGGERED CONTROLLED INSULIN RELEASE

Type 1 diabetes mellitus (T1DM) requires exogenous insulin replacement, and stimuli-responsive implantable systems may contribute to alternative delivery strategies. This study aimed to develop a nano-in-micro system of alginate microspheres containing iron oxide magnetic nanoparticles (Fe₃O₄), regular human insulin, and chitosan, designed for insulin release under external magnetic stimulation. The stability of microspheres crosslinked with CaCl₂, SrCl₂, or FeCl₃ was evaluated by swelling assays in EDTA and PBS. Biocompatibility and biodegradation of insulin-free formulations at the subcutaneous implantation site were assessed over 35 days (days 1, 7, 14, 21, 28 and 35) in euglycemic mice, with one animal per time point and 2–4 microspheres weighed individually per animal. For functional evaluation, T1DM was induced in C57BL/6J mice by intravenous alloxan, and an animal with blood glucose >350 mg/dL received a subcutaneous implant of the CaCl₂-crosslinked formulation containing insulin and magnetic nanoparticles, followed by glycemic monitoring under magnetic stimulation (n = 1; three stimuli on different days). Procedures were approved by the Animal Ethics Committee (CEUA), protocol no. 01200.001568/2013-87.

All three formulations (CaCl₂, SrCl₂, and FeCl₃) showed only modest absorption, with minimal mass loss and no complete absorption of the microspheres throughout the 35-day follow-up. In the diabetic animal, blood glucose decreased after each of three magnetic stimuli applied on different days (days 1, 2 and 3), indicating the functional activity of insulin released in vivo. These preliminary results suggest the feasibility of magnetoresponsive alginate microspheres as a platform for externally triggered insulin release, with potential for subcutaneous application.