Formulation and physiologic factors affecting the pharmacology of carrier-mediated anticancer agents

Abstract

Introduction: Major advances in carrier-mediated agents (CMAs), which include nanoparticles and conjugates, have revolutionized drug delivery capabilities over the past decade. While providing numerous advantages such as increased exposure duration, greater solubility and delivery to tumor sites over their small molecule counterparts, there is substantial variability in how individual CMA formulations affect the pharmacology, pharmacokinetics and pharmacodynamics (efficacy and toxicity) of these agents.

Areas covered: CMA formulations are complex in nature compared to their small molecule counterparts and consist of multiple components and variables that can affect the pharmacological profile. This review provides an overview of factors that affect the pharmacologic profiles observed in CMA-formulated chemotherapy, primarily in liposomal formulations, that are currently in preclinical or early clinical development.

Expert opinion: Despite the numerous advantages that CMA formulations provide, their clinical use is still in its infancy. It is critical that we understand the mechanisms and effects of CMAs in navigating biological barriers and how these factors affect their biodistribution and delivery to tumors. Future studies are warranted to better understand the complex pharmacology and interaction between CMA carriers and biological systems, such as the mononuclear phagocyte system and tumor microenvironment.

Keywords:

• chemotherapy
• carrier-mediated agents
• drug delivery
• mononuclear phagocyte system
• nanomedicine
• nanoparticles
• tumor targeting

Declaration of interest

WC Zamboni holds equity in and licensed patent on MPS probe to Wildcat Pharmaceutical Development Center. Work performed by authors is partially supported by NIH/NCI (1 U54 CA151652-01) Carolina Center of Cancer Nanotechnology Excellence and the UNC University Cancer Research Fund. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors have no other 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 apart from those disclosed.

Notes

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