Nanocochleates as the Potential Delivery Systems for Oral Antitumor of Hydroxycamptothecin.

: It remains a major challenge to improve the oral antitumor efficacy of hydroxycamptothecin (HCPT). The aim of this study was to develop the oral HCPT formulation via nanocochleates technology. After HCPT was incorporated into calcium ions-induced nanocochleates, its oral bioavailability significantly enhanced, up to a 2.3-fold. Most importantly, in vivo antitumor effect of HCPT-loaded nanocochleates could be achieved upon oral administration to hepatoma-bearing BALB/c-nude mice, showing the remarkable inhibition of tumor growth as compared to normal saline, HCPT suspensions and HCPT-loaded liposomes. Caco-2 cells, as an in vitro model, were conducted to investigate the absorption mechanisms of intestinal tract. Caco-2 transport studies indicated that HCPT-loaded nanocochleates were uptake via clathrin- and caveolin-mediated endocytosis. Furthermore, ZO-1, F-actin and claudin-4, known as three cellular tight junction proteins, were obvious down-regulation, which suggested that HCPT-loaded nanocochleates could open cellular tight junctions and paracellular route. In conclusion, nanocochleates served as a promising vehicle to facilitate the oral delivery of HCPT.