Lipid nanocarrier system for bioavailability enhancement of tacrolimus

Abstract

The present study dealt with development of TL loaded NLCs incorporating lipids newlineand surfactants having P-gp inhibitory and immunosuppressive characteristic properties by a novel low energy method to overcome the biopharmaceutical challenges associated with efficient oral delivery of TL, and assessment of their performance in vivo (which include TL solubilisation across enterocyte, lymphatic and systemic accessibility as shown in Figure 1). newlineThe present study revealed that the concentration of TL in blood and lymph were significantly improved attributed to the MCT-cum-LCT based matrix structural composition of NLCs. The study findings confirmed that by blocking the lymphatic route, bioavailability of TL can be very newlinewell predicted via in vitro lipolysis experiments. newlineThe results of lymphatic distribution study demonstrated significantly higher lymphatic accessibility of fish oil integrated F-NLC in comparison to N-NLC (without fish oil) and TL suspension (***plt0.001) which could lead to promising therapeutic outcome in newlineimmunosuppressive drug therapy. Furthermore the present study intricately demonstrated that fatty acid chain length or to be more precise, MCT and LCT based lipids could result in markedly different and characteristically enhanced solubilisation, absorption and distribution prospects of TL in vivo. The in vitro IL-2 cytokine profiling experiment results confirmed that newlineincorporation of fish oil in TL-NLC not only enhances TL accessibility to its site of action which is lymph but also widen its therapeutic activity by potentiating its immunosuppressive action. newline16 newlineTo conclude, the lymphatic concentration profile of TL (which is the site of action of TL) was tremendously enhanced by means of developed TL-NLC formulation which opens potential therapeutic fronts in immunosuppressive drug therapy.