Entrapment and release kinetics of furosemide from pegylated nanocarriers

Abstract

This study was designed to test the hypothesis that furosemide (Fur) can be entrapped into surfactant free pegylated nanocarriers (NCs) for controlled drug release. To test this hypothesis, Fur-loaded NCs were prepared by emulsion solvent diffusion method. A 23 factorial design was used to optimize the effect of three formulation variables [amounts of Fur (X1), poly(lactic-co-glycolic acid) (X2) and poly-ɛ-caprolactone-polyethylene glycol (X3)] on particle mean diameter (Y1), polydispersity index (PDI, Y2), and percent drug encapsulation efficiency (EE%, Y3). The NCs were characterized for morphology, thermal behavior, optical properties, crystallinity, and drug release kinetics using electron microscopy (EM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (PXRD), and high performance liquid chromatography, respectively. The optimum formula produced with 6mg of Fur, 7mg of PLGA, and 1mg of PCL–PEG corresponded to 183.26nm, 0.26, and 88.29% as Y1, Y2 and Y3 values, respectively. DSC thermograms, FTIR spectra and PXRD diffractograms indicated that Fur was encapsulated in its polymorphic crystalline form I within the NCs polymeric matrix. This was further confirmed by a comparative study between native Fur, Fur nanocrystal and Fur loaded NCs using scanning EM, PXRD and drug release kinetics. The release kinetics of the optimized formula fit the Higuchi model indicating that the drug was released by diffusion in 12h. These results indicate that pegylated Fur-loaded NCs could be successfully prepared with high EE% and sustained release profile intended for the inner ear drug delivery.