Paclitaxel, which features low water solubility and permeability, is an efflux pump substrate. The current paclitaxel drugs are given intravenously after resolving the solubility issue. Yet, oral delivery to achieve therapeutic bioavailability is not effective due to low absorption. This study evaluated a natural compound, rubusoside, to improve oral bioavailability in an animal model. Free paclitaxel molecules were processed into nano-micelles formed in water with rubusoside. The particle size of the nano-micelles in water was determined using dynamic light scattering. The oral bioavailability of paclitaxel in nano-micelles was determined against Cremophor/alcohol-solubilized Taxol after oral and intravenous administration to pre-cannulated Sprague Dawley rats. When loaded into the rubusoside-formed nano-micelles, paclitaxel reached a supersaturated concentration of 6 mg/mL, 60,000-fold over its intrinsic saturation of 0.1 µg/mL. The mean particle size was 4.7 ± 0.7 nm in diameter. Compared with Taxol^®, maximum blood concentration was increased by 1.5-fold; the time to reach maximum concentration shortened to 0.8 h from 1.7 h; and, relative oral bioavailability increased by 88%. Absolute oral bioavailability was 1.7% and 1.3% for the paclitaxel nano-micelles and Taxol^®, respectively. Solubilizing paclitaxel with rubusoside was successful, but oral bioavailability remained low. Further inhibition of the efflux pump and/or first metabolism may allow more oral paclitaxel to enter systemic circulation.

Aim: To examine if rubusoside (RUB) can overcome insolubility of betulonic acid (BEA), it can be accurately evaluated for its intrinsic activity against cancer in cell culture and in tumor animal models. Materials & methods: By processing RUB and BEA together using a solvent evaporation method, a joint nanoparticulate structure is formed, designated as BEA-NP. Results: BEA-NP was found over three-times more permeable than that solubilized by DMSO in Caco-2 cell monocultures. In an in vivo efficacy study, the tumor growth in the S180 berry mice orally dosed with BEA-NP at 75 mg/kg was inhibited by 50%. Conclusion: RUB was effective in solubilizing BEA, maintaining its cytotoxicity, enhancing its permeability and reducing tumor growth when orally administered.