Drug delivery design for intravenous route with integrated physicochemistry, pharmacokinetics and pharmacodynamics: illustration with the case of taxane therapeutics

Abstract

This review is aimed at combining the published data on taxane formulations into a generalized Drug Delivery approach, starting from the physicochemistry and assessing its relationships with the pharmacokinetics, the biodistribution and the pharmacodynamics. Owing to the number and variety of taxane formulation designs, we considered this class of cytotoxic anticancer agents of particular interest to illustrate the concepts attached to this approach. According to the history of taxane development, we propose a classification as (i) "surfactant-based formulations" first generation, (ii) "surfactant-free formulations" second generation and (iii) "modulated pharmacokinetics drug delivery systems" third generation. Since our objective was to make the link between (i) the physicochemistry of the drug and carrier and (ii) the efficacy and safety of the drug in preclinical animal models and (iii) in human, we focused on the drug delivery technologies that were tested in clinic.

Keywords: Biopharmacy; Cabazitaxel; Classification; Docetaxel; Drug delivery systems design; Efficacy; Nanoparticles; Paclitaxel; Pharmacodynamics; Pharmacokinetics; Physicochemistry; Safety; Taxanes.