Absorption mechanism of DHP107, an oral paclitaxel formulation that forms a hydrated lipidic sponge phase

Abstract

Paclitaxel is a most widely used anticancer drug with low oral bioavailability, thus it is currently administered via intravenous infusion. DHP107 is a lipid-based paclitaxel formulation that can be administered as an oral solution. In this study, we investigated the mechanism of paclitaxel absorption after oral administration of DHP107 in mice and rats by changing the dosing interval, and evaluated the influence of bile excretion. DHP107 was orally administered to mice at various dosing intervals (2, 4, 8, 12, 24 h) to examine how residual DHP107 affected paclitaxel absorption during subsequent administration. Studies with small-angle X-ray diffraction (SAXS) and cryo-transmission electron microscopy (cryo-TEM) showed that DHP107 formed a lipidic sponge phase after hydration. The AUC values after the second dose were smaller than those after the first dose, which was correlated to the induction of expression of P-gp and CYP in the livers and small intestines from 2 h to 7 d after the first dose. The smaller AUC value observed after the second dose was also attributed to the intestinal adhesion of residual formulation. The adhered DHP107 may have been removed by ingested food, thus resulting in a higher AUC. In ex vivo and in vivo mucoadhesion studies, the formulation adhered to the villi for up to 24 h, and the amount of DHP107 that adhered was approximately half that of monoolein. The paclitaxel absorption after administration of DHP107 was not affected by bile in the cholecystectomy mice. The dosing interval and food intake affect the oral absorption of paclitaxel from DHP107, which forms a mucoadhesive sponge phase after hydration. Bile excretion does not affect the absorption of paclitaxel from DHP107 in vivo.

Thirty Years of Cancer Nanomedicine: Success, Frustration, and Hope

“…On the other hand, intraperitoneally injection proved to be effective in targeting circulating macrophages, which, once repolarized, exhibited inherent tumor tropism [134]. Finally, as demonstrated by the recent approval of DHP107 (Liporaxel ® , DAE HWA Pharm, Seoul, Korea) the oral route has been investigated for increasing patient compliance and reduce the therapy costs [135].…”

Liquid Crystalline Nanostructures as PEGylated Reservoirs of Omega-3 Polyunsaturated Fatty Acids: Structural Insights toward Delivery Formulations against Neurodegenerative Disorders

“…Such carrier particles (cubosomes, hexosomes, or spongosomes) do not rapidly break upon contact with biological fluids after administration and may provide sustained release. 3 , 6 , 24 , 43 , 44 , 49 Moreover, they can be sterically stabilized by hydrophilic shells to avoid eventual aggregation in the milieu. 3 , 10 , 14 , 29 , 47 , 48 …”

Antitumour effects of Liporaxel (oral paclitaxel) for canine melanoma in a mouse xenograft model

“…This drug formulation is absorbed through the gastrointestinal membrane and effectively distributed in major organs . The mucoadhesive formulation of oral paclitaxel improves its permeability …”