Nanoparticle drug loading as a design parameter to improve docetaxel pharmacokinetics and efficacy

Kevin S. Chu, Allison N. Schorzman, Mathew C. Finniss, Charles J. Bowerman, Lei Peng, James C. Luft, Andrew J. Madden, Andrew Z. Wang, William C. Zamboni, Joseph M. DeSimone

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

Nanoparticle (NP) drug loading is one of the key defining characteristics of an NP formulation. However, the effect of NP drug loading on therapeutic efficacy and pharmacokinetics has not been thoroughly evaluated. Herein, we characterized the efficacy, toxicity and pharmacokinetic properties of NP docetaxel formulations that have differential drug loading but are otherwise identical. Particle Replication in Non-wetting Templates (PRINT®), a soft-lithography fabrication technique, was used to formulate NPs with identical size, shape and surface chemistry, but with variable docetaxel loading. The lower weight loading (9%-NP) of docetaxel was found to have a superior pharmacokinetic profile and enhanced efficacy in a murine cancer model when compared to that of a higher docetaxel loading (20%-NP). The 9%-NP docetaxel increased plasma and tumor docetaxel exposure and reduced liver, spleen and lung exposure when compared to that of 20%-NP docetaxel.

Original languageEnglish (US)
Pages (from-to)8424-8429
Number of pages6
JournalBiomaterials
Volume34
Issue number33
DOIs
StatePublished - Nov 2013
Externally publishedYes

Keywords

  • Docetaxel
  • Drug loading
  • Pharmacokinetics
  • Polylactic acid
  • Soft-lithography

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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