Docetaxel Distribution Following Intraperitoneal Administration in Mice

摘要: Purpose: Intraperitoneal (IP) chemotherapy with high molecular weight lipophilic antineoplastic agents such as the taxanes has shown promise in clinical trial evaluation for treatment of localized peritoneal cancers. We have previously developed an IP injectable hydrogel formulation (PoLigel) sustained delivery docetaxel (DTX), and observed significant efficacy murine models ovarian cancer when compared to Taxotere®, FDA approved DTX. In order understand relationship between drug distribution efficacy, current study compares tissue pharmacokinetics DTX administered PoLigel or Taxotere® formulations. Methods: The was prepared by blending a water-soluble chitosan derivative, egg phosphatidylcholine lauric aldehyde (drug material ratio 1:8 w/w). concentrations plasma, heart, liver, spleen, stomach, intestine, kidney muscle were measured over five day period following administration formulations CD-1 female mice. Results: Three days after administration, no detectable levels seen while plasma 0.06 ug/ml ± 0.01 per PoLigel. At post only stomach showed whereas all tissues mice that received resulted from significantly higher cavity 200 fold than found plasma. Conclusions: Overall, increases retention provides clinically used formulation. may be responsible improvement been our previous studies.