Podophyllotoxin is a natural compound belonging to the lignan family and
is well-known for its great antitumor activity. However, it shows several limitations,
such as severe side effects and some pharmacokinetics problems, including low water
solubility, which hinders its application as an anticancer agent. Over the past few years,
antitumor research has been focused on developing nanotechnology-based medicines
or nanomedicines which allow researchers to improve the pharmacokinetic properties
of anticancer compounds. Following this trend, podophyllotoxin nanoconjugates have
been obtained to overcome its biopharmaceutical drawbacks and to enhance its antitumor
properties. The objective of this review is to highlight the advances made over the past
few years (2017–2023) regarding the inclusion of podophyllotoxin in different nanosystems.
Among the huge variety of nanoconjugates of diverse nature, drug delivery systems bearing
podophyllotoxin as cytotoxic payload are organic nanoparticles mainly based on polymer
carriers, micelles, and liposomes. Along with the description of their pharmacological
properties as antitumorals and the advantages compared to the free drug in terms of
biocompatibility, solubility, and selectivity, we also provide insight into the synthetic
procedures developed to obtain those podophyllotoxin-nanocarriers. Typical procedures
in this regard are self-assembly techniques, nanoprecipitations, or ionic gelation methods
among others. This comprehensive perspective aims to enlighten the medicinal chemistry
community about the tendencies followed in the design of new podophyllotoxin-based
drug delivery systems, their features and applications.
