Seek and destroy: improving PK/PD profiles of anticancer agents with nanoparticles

Expert Review of Clinical Pharmacology
Anne RodallecJoseph Ciccolini

Abstract

The Pharmacokinetics/pharmacodynamics (PK/PD) relationships with cytotoxics are usually based on a steepening concentration-effect relationship; the greater the drug amount, the greater the effect. The Maximum Tolerated Dose paradigm, finding the balance between efficacy, while keeping toxicities at their manageable level, has been the rule of thumb for the last 50-years. Developing nanodrugs is an appealing strategy to help broaden this therapeutic window. The fact that efficacy and toxicity with cytotoxics are intricately linked is primarily due to the complete lack of specificity toward the tumor tissue during their distribution phase. Because nanoparticles are expected to better target tumor tissue while sparing healthy cells, accumulating large amounts of cytotoxics in tumors could be achieved in a safer way. Areas covered: This review aims at presenting how nanodrugs present unique features leading to reconsidering PK/PD relationships of anticancer agents. Expert commentary: The constant interplay between carrier PK, interactions with cancer cells, payload release, payload PK, target expression and target engagement, makes picturing the exact PK/PD relationships of nanodrugs particularly challenging. However, those improv...Continue Reading

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Citations

Oct 26, 2018·Expert Opinion on Drug Metabolism & Toxicology·Anne RodallecJoseph Ciccolini
Jul 7, 2020·Frontiers in Pharmacology·Shihori TanabeRyuichi Ono
Nov 20, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Rodrigo S HeyderSandro R P da Rocha
Aug 21, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Mélanie DonnetteRaphaelle Fanciullino
Feb 25, 2020·Advanced Drug Delivery Reviews·A L B SeynhaeveT L M Ten Hagen

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