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Plasma Stability and Plasma Metabolite Concentration-Time Profiles of Oligo(Lactic Acid)8-Paclitaxel Prodrug Loaded Polymeric Micelles

  1. Author:
    Repp, Lauren
    Skoczen,Sarah
    Rasoulianboroujeni, Morteza
    Stern,Steve
    Kwon, Glen S

  2. Author Address

    Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, Wisconsin, 53705, USA., Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research Sponsored By the National Cancer Institute, Frederick, Maryland, 21702, USA., Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, Wisconsin, 53705, USA. glen.kwon@wisc.edu.,
    1. Year: 2023
    2. Date: Apr 11
    3. Epub Date: 2023 04 11
  2. Journal: The AAPS Journal
    1. 25
    2. 3
    3. Pages: 39
  4. Type of Article: Article
  5. Article Number: 39
  1. Abstract:

    Paclitaxel (PTX) is a frequently prescribed chemotherapy drug used to treat a wide variety of solid tumors. Oligo(lactic acid)8-PTX prodrug (o(LA)8-PTX) loaded poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA) micelles have higher loading, slower release and higher antitumor efficacy in murine tumor models over PTX-loaded PEG-b-PLA micelles. The goal of this work is to study plasma stability of o(LA)8-PTX-loaded PEG-b-PLA micelles and its pharmacokinetics after IV injection in rats. In rat plasma, o(LA)8-PTX prodrug is metabolized into o(LA)1-PTX and PTX. In human plasma, o(LA)8-PTX is metabolized more slowly into o(LA)2-PTX, o(LA)1-PTX, and PTX. After IV injection of 10 mg/kg PTX-equiv of o(LA)8-PTX prodrug loaded PEG-b-PLA micelles in Sprague-Dawley rats, metabolite abundance in plasma follows the order: o(LA)1-PTX > o(LA)2-PTX > o(LA)4-PTX > o(LA)6-PTX. Bile metabolite profiles of the o(LA)8-PTX prodrug is similar to plasma metabolite profiles. In comparison to equivalent doses of Abraxane®, plasma PTX exposure is two orders of magnitude higher for Abraxane® than PTX from o(LA)8-PTX prodrug loaded PEG-b-PLA micelles, and plasma o(LA)1-PTX exposure is fivefold higher than PTX from Abraxane®, demonstrating heightened plasma metabolite exposure for enhanced antitumor efficacy.

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  2. DOI: 10.1208/s12248-023-00807-4
  3. PMID: 37041376
  4. PII : 10.1208/s12248-023-00807-4

Library Notes

  1. Fiscal Year: FY2022-2023
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