Fabrication of levan/gellan gum nanocomposite hydrogels containing dexamethasone-loaded albumin nanoparticles for controlled release application

Abstract

In this study, nanocomposite hydrogels were produced as a new drug delivery system. Firstly, three different composite hydrogels (Le/GG-1, Le/GG-2 and Le/GG-3) were produced by combining Levan (Le) obtained from Halomonas elongata 153B and Gellan gum (GG) with different amounts of 1,4-Butanedioldiglycidyl ether (BDDE) crosslinker. The rheological and physicochemical properties of the composite hydrogels were characterized and the average pore size of LE/GG-1 (low crosslinker amount) was determined to be 245.51 nm, Le/GG-2 was 193.62 nm and Le/GG-3 (high crosslinker amount) was 169.72 nm. It was determined that the swelling (%) of the composite hydrogels increased with temperature and the hydrogel with a higher amount of crosslinker (Le/ GG-3) had a slower swelling (17.94 % swelling at the end of 72 h at 45 degrees C) and slower degradation (47.4 % mass remaining at the end of 72 h at 45 degrees C) due to its smaller pore size. Dexamethasone (DEX) was loaded onto albumin nanoparticles by the desolvation method to obtain DEX-loaded albumin nanoparticles (DEX-AlNps) (average particle size: 155 nm and (PdI): 0.21). It was determined that DEX from DEX-AlNps was released faster in acidic medium in the presence of lysozyme, while it was released slower and in a controlled manner in basic medium (79.7 % was released at pH 5.0, 61.6 % at pH 6.5 and 53.3 % at pH 7.4) and the release kinetics occurred according to the Hixson-Crowell model. Finally, 81.3 % DEX-AlNps was loaded into Le/GG-1 composite hydrogel, 70.4 % into Le/GG-2 and 54.2 % into Le/GG-3 to obtain nanocomposite hydrogels. At the end of 48 h, 54.8 % DEX was released from Le/GG-1 composite hydrogel, 33.8 % from Le/GG-2 and 24.2 % from Le/GG-3 in PBS medium (pH 7.4) containing lysozyme. Thus, it was revealed that the amount of drug loaded and the release rates changed depending on the change in the amount of crosslinker in the obtained nanocomposite hydrogels.