Distribution and Accumulation Characteristics of Five Pulchinenosides in Tumor-Bearing Mice for Solubilization Formulations Using LC-ESIMS/ MS Method

Background: A growing attention was paid on the antitumor activities of Pulsatilla chinensis (Bunge) Regel. For better pharmacological elucidation and further safety evaluation, we characterized tissue distribution of five active pulchinenosides for solubilization formulations of Pulsatilla chinensis saponins in a tumour-bearing mice model. Hypothesis/Purpose: The active ingredients level at the site of action tissues is the relevant measure of drug effect. Especially for antitumor drug formulations, their biodistributions are crucial to investigating the target tissues and potential accumulative organs. Study Design: Tissue distributions of the various water-solution formulations delivering saponins in vivo were taken for the first time. In addition, to evaluate probability of tissues accumulation, active components levels in various organs were investigated after a long-term administration. Methods: The extract of PRS was prepared for PRS-Na, PRS-HPβCD, PRS-O/W, PRS-silica, PRS-Na- HPβCD, respectively. Heterotopic transplanted liver tumor model mice were adopted. The PRS levels of tissues were determined by HPLC-MS/MS method. Results: PRS-Na was a suitable oral formulation for saponins treating cancer. Lung was potential target tissue for PRS-O/W, while liver for PRS- HPβCD, and PRS-Na-HPβCD. Among all the designed formulations, PRS-micronized silica was most unsuitable for saponins treating liver cancer. Besides, low dosage (80mg/kg) daily administrated to mice not showed significant tissue accumulation. However, fat storage would be noticed in high dosage (300mg/kg) of PRS-Na, PRS- HPβCD, and lung of PRS- micronized silica formulation. Conclusion: Disposition into target tissues plays an important role for pharmacological effects, especially for natural compounds. Based on the results of pharmacokinetics and distribution results, PRS-Na was a suitable oral formulation for saponins treating cancer. Fat accumulation for long-term administration was not ignored for saponins formulations. Keywords: Saponins, distribution, accumulation, solubilization formulations, tumor, pulchinenosides.