Preparation of a MVL-Ca-Alg/CS MEMs system with add-on effect for type 2 diabetes treatment

Add-on drugs, often called as synergistic therapy, for diabetes have been comparatively more promising as they can reduce the systemic adverse effects resulted during respective monotherapy [metformin (MET)/insulin (INS)]. Herewith, we formulated a multivesicular liposome microparticles-embedded Ca-Alg/chitosan microcapsules (MVL-Ca-Alg/CS MEMs) system by a double-emulsion method using a high voltage electrostatic droplet generator. Physical characterization of the designed formulation was elucidated based on particle size and distribution, drug loading and encapsulation efficiency, drug delivery properties, and pharmacodynamic evaluation. The multivesicular liposomes microparticles (MVLs MPs) and MVL-Ca-Alg/CS MEMs have shown good sphericity and dispersion, and the average diameters were 37 and 491?µm, respectively. The confocal laser scanning microscopic observations demonstrated that fluorescein isothiocyanate-conjugated INS is uniformly dispersed in MVLs MPs, predominantly within the lumen of the polycystic liposome. This multicomponent system possessing INS in the inner space and MET at the outer space resulted in orderly and sustained drug release patterns. Furthermore, the obtained in vivo experimental data have shown that the designed MEMs system resulted in significantly higher hypoglycemic effect compared to pure INS, demonstrating that our multicomponent design has an enormous potential for treating diabetes.