Formulation design, characterization, and in vitro and in vivo evaluation of nanostructured lipid carriers containing a bile salt for oral delivery of gypenosides

BACKGROUND: Gypenosides (GPS) have been used as traditional medicine for centuries with various pharmacological effects. However, its therapeutic effects were restricted owing to the poor lipid and water solubility and low absorption. This study aimed to develop nanostructured lipid carriers (NLCs) containing a bile salt formulation (sodium glycocholate, SGC) for GPS, and to evaluate the potential of the GPS-SGC-NLCs as an oral delivery system. METHODS: The preparation of GPS-SGC-NLCs was investigated using a single-factor test and a central composite design of response surface methodology. In vitro release and pharmacokinetics studies were used to evaluate the dissolution and bioavailability of GPS. Furthermore, In vivo imaging and in situ intestinal perfusion studies were performed to investigate the absorption of the preparations in the gastrointestinal tract. RESULTS: The optimised formulation yielded nanoparticles with an approximate diameter of 146.7 nm, polydispersity of 0.137, zeta potential of −56.0 mV, entrapment efficiency of 74.22% and drug loading of 4.89%. An in vitro dissolution analysis revealed the sustained release of contents from GPS-SGC-NLCs over 48 h with 56.4% of the drug released. A pharmacokinetic analysis revealed an 8.5-fold increase of bioavailability of the GPS-SGC-NLCs compared with GPS powder. In vivo imaging and in situ intestinal perfusion studies showed that SGC-NLCs could significantly increase the absorption of GPS in intestinal tract. In vitro cytotoxicity evaluated using Caco-2 cells demonstrated that GPS-SGC-NLCs decrease the cytotoxicity of the drug. CONCLUSION: The SGC-NLC formulation can significantly improve the absorption of GPS, which provides an effective approach for enhancing the oral absorption of drugs.