Bilosomes: A controlled delivery system for the sustained release of torularhodin during digestion in the small intestine both in vitro and in vivo

Torularhodin is a carotenoid with various biological activities, but its poor chemical stability and low bioavailability are obstacles to its usage. In this study, different small intestinal controlled delivery systems of torularhodin; including liquid-lip, liposomes, niosomes, and bilosomes; were prepared and characterized. Then, in vitro simulated gastrointestinal digestion model and in vivo mouse model were used to evaluate their sustained-release properties. Finally, mathematical models such as release kinetics revealed the release mechanisms of different systems. The results of particle size distribution and release rate of torularhodin indicated that both the liquid-lip and liposomes systems were almost completely digested after 2 h of simulated small intestinal digestion. However, the bilosomes system remained intact after simulated gastric digestion and were slowly cleaved during simulated small intestinal digestion with a sustained release effect of torularhodin. The fitting results of six kinetic models demonstrated that the kinetic mechanism of torularhodin release from bilosomes was a non-fickian mechanism. The main mechanism may be that bilosomes enhance the permeability of enterocyte biofilms by opening tight junctions between intestinal epithelial cells, thereby prolonging the release of torularhodin in the small intestine. Pharmacokinetic results in mice showed that the area under the concentration time curve in the bilosomes system was 2.73 times that of the liquid-lip system, and the t 1/2 was as long as 22.5 h, demonstrating that bilosomes system was an efficient delivery system for enhancing both the stability and bioavailability of torularhodin in the small intestine. These findings can be used to help future potential applications of bilosomes delivery systems for improving the bioavailability of carotenoids in food. • Liquid-lip, liposomes, niosomes, and bilosomes were evaluated in vitro and in vivo • Torularhodin in bilosomes behaved a sustained release effect with high stability • Kinetic mechanism of bilosomes release torularhodin was a non-Fickian mechanism in vitro • Bilosomes enhanced bioavailability of torularhodin in small intestine pharmacokinetic in vivo • Applications of bilosomes can improve the bioavailability of carotenoids in food