Improved oral bioavailability of notoginsenoside R1 with sodium glycocholate-mediated liposomes: Preparation by supercritical fluid technology and evaluation in vitro and in vivo

摘要

The chief objective of this research was to appraise liposomes embodying a bile salt, sodium glycocholate (SGC), as oral nanoscale drug delivery system to strengthen the bioavailability of a water-soluble and weakly penetrable pharmaceutical, notoginsenoside R1 (NGR1). NGR1-loaded liposomes were prepared with the improved supercritical reverse evaporation (ISCRPE) method and the preparation conditions were optimized with response surface methodology (RSM). The mean encapsulation efficiency (EE), particle size, and polydispersity index (PDI) of the optimized liposomal formulation (NGR1@Liposomes) were 49.49%, 308.3 nm, and 0.229, respectively. SGC-mediated liposomes (NGR1@SGC-Liposomes) were formulated based on the optimal preparation conditions and the mean EE, particle size, and PDI were 41.51%, 200.1 nm, and 0.130, respectively. The in vitro Caco-2 cellular uptake of fluorescent marker was increased by loading into NGR1@SGC-Liposomes as compared with the conventional liposomes. Furthermore, the intestinal permeability as well as the intestinal absorption of NGR1 were both significantly improved with NGR1@SGC-Liposomes as the nanovesicles. The in vivo pharmacokinetic study results showed that AUC(0-t) value of NGR1@SGC-Liposomes and NGR1@Liposomes was 2.68and 2.03-fold higher than that of NGR1 aqueous solution, respectively. The AUC(0-t) of the NGRl@SGC-Liposomes group was significantly higher than that of NGR1@Liposomes. Thus, ISCRPE method is a feasible method for the preparation of water-soluble drug-loaded liposomes and bile salt-mediated liposomes may enhance the oral absorption of water-soluble and poorly permeable drugs.