Metformin-Loaded Polymer-Based Microbubbles/Nanoparticles Generated for the Treatment of Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is a chronic metabolicdisease that is increasingly common all over the world with a high risk ofprogressive hyperglycemia and high microvascular and macrovascularcomplications. The currently used drugs in the treatment of T2DM haveinsufficient glucose control and can carry detrimental side effects. Severaldrug delivery systems have been investigated to decrease the side effectsand frequency of dosage, and also to increase the effect of oralantidiabetic drugs. In recent years, the use of microbubbles in biomedicalapplications has greatly increased, and research into microactive carrierbubbles continues to generate more and more clinical interest. In thisstudy, various monodisperse polymer nanoparticles at differentconcentrations were produced by bursting microbubbles generatedusing a T-junction microfluidic device. Morphological analysis byscanning electron microscopy, molecular interactions between the components by FTIR, drug release by UV spectroscopy, andphysical analysis such as surface tension and viscosity measurement were carried out for the particles generated and solutions used.The microbubbles and nanoparticles had a smooth outer surface. When the microbubbles/nanoparticles were compared, it wasobserved that they were optimized with 0.3 wt % poly(vinyl alcohol) (PVA) solution, 40 kPa pressure, and a 110 mu L/minflow rate,thus the diameters of the bubbles and particles were 100 +/- 10 mu m and 70 +/- 5 nm, respectively. Metformin was successfully loadedinto the nanoparticles in these optimized concentrations and characteristics, and no drug crystals and clusters were seen on thesurface. Metformin was released in a controlled manner at pH 1.2 for 60 min and at pH 7.4 for 240 min. The process and structuresgenerated offer great potential for the treatment of T2DM.