Chitosan nanoparticles as promising tool for berberine delivery: Formulation, characterization and in vivo evaluation

Berberine chloride (BER) is a benzylisoquinoline alkaloid known for its antihypertensive, antihyperglycemic, antitumor, anti-inflammatory and antioxidant activities. BER has limited absorption from the gastrointestinal tract due to self-aggregation, P-glycoprotein-mediated efflux and hepatobiliary re-excretion; therefore, its oral bioavailability is very low. The aim of this study is to develop BER loaded chitosan nanoparticles (BER-NPs) in order to increase the oral bioavailability and gastrointestinal stability of BER. BER-NPs were prepared by ionotropic gelation method. In order to characterize the formulation, encapsulation efficiency, particle size, polydispersity index and zeta potential were determined. At the end of the analysis the encapsulation efficiency was found to be 31.5 ± 0.4%, the zeta potential 41.6 ± 0.8 mV, the particle size 406 ± 25 nm and the polydispersity index was 0.462 ± 0.105. BER-NPs were also morphologically visualized by transmission electron microscopy (TEM) and characterized by Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC) analysis. In addition, solubility, dissolution and partition coefficient of BER and BER-NPs were determined and evaluated. In the in vitro drug release study, it was observed that BER was initially released rapidly from the formulation and then the release continued in a controlled manner. Stability studies have shown that BER-NPs increase the stability of BER in simulated gastrointestinal fluids. In addition, long term stability analyses were also performed and it was found that it would be appropriate to store BER-NPs at 5 °C ± 3 °C. The maximum plasma concentration (Cmax) for BER-NPs was found to be 32.7 ± 3.0 ng/mL in in vivo experiments in rats. The relative bioavailability of BER-NPs was calculated as 122.06%.