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

ABSTRACT

Introduction: 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 improved PK/PD relationships now make the once contradictory higher efficacy and lower toxicities requirement an achievable goal in cancer patients.

KEYWORDS:

• Nanoparticles
• Pharmacokinetics
• cancer
• PK/PD
• drug delivery

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.