Bioconjugation of Podophyllotoxin and Nanosystems: Approaches for Boosting Its Biopharmaceutical and Antitumoral Profile

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 anticanc...

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Main Authors: Carolina Miranda-Vera, Ángela-Patricia Hernández, Pilar García-García, David Díez, Pablo A. García, María Ángeles Castro
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/2/169
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author Carolina Miranda-Vera
Ángela-Patricia Hernández
Pilar García-García
David Díez
Pablo A. García
María Ángeles Castro
author_facet Carolina Miranda-Vera
Ángela-Patricia Hernández
Pilar García-García
David Díez
Pablo A. García
María Ángeles Castro
author_sort Carolina Miranda-Vera
collection DOAJ
description 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.
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spelling doaj-art-0993a46f29c94de8a01b4d5fa3722f592025-08-20T02:03:30ZengMDPI AGPharmaceuticals1424-82472025-01-0118216910.3390/ph18020169Bioconjugation of Podophyllotoxin and Nanosystems: Approaches for Boosting Its Biopharmaceutical and Antitumoral ProfileCarolina Miranda-Vera0Ángela-Patricia Hernández1Pilar García-García2David Díez3Pablo A. García4María Ángeles Castro5Laboratorio de Química Farmacéutica, Departamento de Ciencias Farmacéuticas, CIETUS, IBSAL, Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37007 Salamanca, SpainLaboratorio de Química Farmacéutica, Departamento de Ciencias Farmacéuticas, CIETUS, IBSAL, Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37007 Salamanca, SpainLaboratorio de Química Farmacéutica, Departamento de Ciencias Farmacéuticas, CIETUS, IBSAL, Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37007 Salamanca, SpainDepartamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad de Salamanca, 37008 Salamanca, SpainLaboratorio de Química Farmacéutica, Departamento de Ciencias Farmacéuticas, CIETUS, IBSAL, Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37007 Salamanca, SpainLaboratorio de Química Farmacéutica, Departamento de Ciencias Farmacéuticas, CIETUS, IBSAL, Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37007 Salamanca, SpainPodophyllotoxin 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.https://www.mdpi.com/1424-8247/18/2/169podophyllotoxinantitumoralnanoparticlespolymer-based drug carriersmicellesliposomes
spellingShingle Carolina Miranda-Vera
Ángela-Patricia Hernández
Pilar García-García
David Díez
Pablo A. García
María Ángeles Castro
Bioconjugation of Podophyllotoxin and Nanosystems: Approaches for Boosting Its Biopharmaceutical and Antitumoral Profile
Pharmaceuticals
podophyllotoxin
antitumoral
nanoparticles
polymer-based drug carriers
micelles
liposomes
title Bioconjugation of Podophyllotoxin and Nanosystems: Approaches for Boosting Its Biopharmaceutical and Antitumoral Profile
title_full Bioconjugation of Podophyllotoxin and Nanosystems: Approaches for Boosting Its Biopharmaceutical and Antitumoral Profile
title_fullStr Bioconjugation of Podophyllotoxin and Nanosystems: Approaches for Boosting Its Biopharmaceutical and Antitumoral Profile
title_full_unstemmed Bioconjugation of Podophyllotoxin and Nanosystems: Approaches for Boosting Its Biopharmaceutical and Antitumoral Profile
title_short Bioconjugation of Podophyllotoxin and Nanosystems: Approaches for Boosting Its Biopharmaceutical and Antitumoral Profile
title_sort bioconjugation of podophyllotoxin and nanosystems approaches for boosting its biopharmaceutical and antitumoral profile
topic podophyllotoxin
antitumoral
nanoparticles
polymer-based drug carriers
micelles
liposomes
url https://www.mdpi.com/1424-8247/18/2/169
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