The role of sex as a biological variable in the efficacy and toxicity of therapeutic nanomedicine

Shahriar Sharifi; Giulio Caracciolo; Daniela Pozzi; Luca Digiacomo; Jennifer Swann; Heike E Daldrup-Link; Morteza Mahmoudi

doi:10.1016/j.addr.2021.04.028

The role of sex as a biological variable in the efficacy and toxicity of therapeutic nanomedicine

Adv Drug Deliv Rev. 2021 Jul:174:337-347. doi: 10.1016/j.addr.2021.04.028. Epub 2021 May 4.

Authors

Shahriar Sharifi¹, Giulio Caracciolo², Daniela Pozzi², Luca Digiacomo², Jennifer Swann³, Heike E Daldrup-Link⁴, Morteza Mahmoudi⁵

Affiliations

¹ Department of Radiology and Precision Health Program, Michigan State University, MI, USA.
² Department of Molecular Medicine, Sapienza University of Rome, Italy.
³ Department of Biological Sciences, Lehigh University, PA, USA.
⁴ Department of Radiology, Pediatric Molecular Imaging, Molecular Imaging Program at Stanford, Stanford University, CA, USA; Department of Pediatrics, Pediatric Hematology/Oncology, Lucile Packard Children's Hospital, Stanford University, CA, USA; Stanford Cancer Institute, Stanford University, CA, USA. Electronic address: H.E.Daldrup-Link@stanford.edu.
⁵ Department of Radiology and Precision Health Program, Michigan State University, MI, USA; Mary Horrigan Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital, Harvard Medical School, MA, USA. Electronic address: mahmou22@msu.edu.

PMID: 33957181
DOI: 10.1016/j.addr.2021.04.028

Abstract

Males and females have physiological, hormonal, and genetic differences that can cause different responses to medicinal treatments. The role of sex in the pharmacokinetics and pharmacodynamics of drugs is well established in the literature. However, researchers have yet to robustly and consistently consider the impact of sex differences on the pharmacokinetics and pharmacodynamics of nanomedicine formulations when designing nanomedicine therapeutics and/or constructing clinical trials. In this review, we highlight the physiological and anatomical differences between sexes and discuss how these differences can influence the therapeutic efficacy, side effects, and drug delivery safety of nanomedicine products. A deep understanding of the effects of sex on nano-based drug delivery agents will robustly improve the risk assessment process, resulting in safer formulations, successful clinical translation, and improved therapeutic efficacies for both sexes.

Keywords: Nanomedicine; Sex-specific response; Therapeutic efficacy.

Publication types

Review

MeSH terms

Animals
Chemistry, Pharmaceutical / methods
Drug Delivery Systems*
Drug Design*
Drug-Related Side Effects and Adverse Reactions / epidemiology
Female
Humans
Male
Nanomedicine
Nanoparticles*
Pharmacokinetics
Sex Factors