Tacrolimus-loaded chitosan-coated nanostructured lipid carriers: preparation, optimization and physicochemical characterization

Tacrolimus as an immunosuppressive drug shows poor solubility in aqueous media, accompanied by a low/variable bioavailability in peroral administration due to its high first-pass metabolism. Therefore, in this study, drug-loaded chitosan-coated nanostructured lipid carriers (CCNLCs) were prepared to overcome these limitations. Tacrolimus-loaded NLCs were prepared via solvent displacement technique and were optimized. Stearic acid (SA) and glyceryl mono stearate (GMS) were used as solid lipids, oleic acid (OA) and tween 80 were used as liquid lipid and stabilizer, respectively, in the structure of NLC. The prepared nanoparticles were characterized by size and zeta potential measurements, drug loading determinations, scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) analysis. Release profile of tacrolimus from NLCs and CCNLCs was also studied. The results indicated the effect of some preparation parameters on particle size as a dependent parameter. The selected formulations had particle sizes under 100 nm. Conversion of negative zeta potential of NLCs into positive quantities in CCNLCs was attributed to the effect of chitosan coating. SEM images of nanocarriers proved nanoscale dimensions and FTIR analysis showed no unwanted chemical reactions between drug and excipients. NLCs and CCNLCs released the drug in a sustained release pattern. However, chitosan-coating attenuated the burst effect and caused more extended release. The results of this study demonstrated formation of tacrolimus-loaded NLCs and coating them with chitosan with desirable characteristics. These findings suggested that this carrier is a good candidate to overcome serious bioavailability problems of common peroral formulations of tacrolimus.