Journal
BIOMATERIALS
Volume 34, Issue 33, Pages 8424-8429Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.07.038
Keywords
Soft-lithography; Docetaxel; Polylactic acid; Drug loading; Pharmacokinetics
Funding
- Carolina Center for Nanotechnology Excellence [U54-CA151652, U54-CA119343]
- University Cancer Research Fund
- Liquidia Technologies, Inc.
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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 (PRIN (R)), 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. (C) 2013 Elsevier Ltd. All rights reserved.
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