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

Publisher： Bentham Science Publishers

E-ISSN： 1875-676x|14|3|175-184

ISSN： 1573-4129

Source： Current Pharmaceutical Analysis, Vol.14, Iss.3, 2018-04, pp. : 175-184

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Abstract

Background: A growing attention was paid on the antitumor activities of Pulsatilla chinensis(Bunge) Regel. For better pharmacological elucidation and further safety evaluation, we characterizedtissue distribution of five active pulchinenosides for solubilization formulations of Pulsatilla chinensissaponins in a tumour-bearing mice model.

Hypothesis/Purpose: The active ingredients level at the site of action tissues is the relevant measure ofdrug effect. Especially for antitumor drug formulations, their biodistributions are crucial to investigatingthe target tissues and potential accumulative organs.

Study Design: Tissue distributions of the various water-solution formulations delivering saponins invivo were taken for the first time. In addition, to evaluate probability of tissues accumulation, activecomponents levels in various organs were investigated after a long-term administration.

Methods: The extract of PRS was prepared for PRS-Na, PRS-HP#946;CD, PRS-O/W, PRS-silica, PRS-Na-HP#946;CD, respectively. Heterotopic transplanted liver tumor model mice were adopted. The PRS levelsof tissues were determined by HPLC-MS/MS method.

Results: PRS-Na was a suitable oral formulation for saponins treating cancer. Lung was potential targettissue for PRS-O/W, while liver for PRS- HP#946;CD, and PRS-Na-HP#946;CD. Among all the designed formulations,PRS-micronized silica was most unsuitable for saponins treating liver cancer. Besides, lowdosage (80mg/kg) daily administrated to mice not showed significant tissue accumulation. However, fatstorage would be noticed in high dosage (300mg/kg) of PRS-Na, PRS- HP#946;CD, and lung of PRS- micronizedsilica formulation.

Conclusion: Disposition into target tissues plays an important role for pharmacological effects, especiallyfor natural compounds. Based on the results of pharmacokinetics and distribution results, PRS-Nawas a suitable oral formulation for saponins treating cancer. Fat accumulation for long-term administrationwas not ignored for saponins formulations.