Nanoparticle drug loading as a design parameter to improve docetaxel pharmacokinetics and efficacy
Kevin S Chu1, Allison N Schorzman, Mathew C Finniss
1Department of Pharmaceutical Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, USA.
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.
Related Concept Videos
Determination of Multiple Dosing Parameters: Loading and Maintenance Doses
Site-Targeted Drug Delivery Systems: Polymeric Carriers
Modified-Release Drug Delivery Systems: Site-Targeted
Bioavailability Enhancement: Drug Permeability Enhancement
Factors Affecting Dissolution: Particle Size and Effective Surface Area
Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions


