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Polymeric Nanoparticle Delivery of Combination Therapy with Synergistic Effects in Ovarian Cancer

Treatment of ovarian cancer is challenging due to late stage diagnosis, acquired drug resistance mechanisms, and systemic toxicity of chemotherapeutic agents. Combination chemotherapy has the potential to enhance treatment efficacy by activation of multiple downstream pathways to overcome drug resis...

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Detalles Bibliográficos
Autores principales: Levit, Shani L., Tang, Christina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072532/
https://www.ncbi.nlm.nih.gov/pubmed/33923947
http://dx.doi.org/10.3390/nano11041048
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author Levit, Shani L.
Tang, Christina
author_facet Levit, Shani L.
Tang, Christina
author_sort Levit, Shani L.
collection PubMed
description Treatment of ovarian cancer is challenging due to late stage diagnosis, acquired drug resistance mechanisms, and systemic toxicity of chemotherapeutic agents. Combination chemotherapy has the potential to enhance treatment efficacy by activation of multiple downstream pathways to overcome drug resistance and reducing required dosages. Sequence of delivery and the dosing schedule can further enhance treatment efficacy. Formulation of drug combinations into nanoparticles can further enhance treatment efficacy. Due to their versatility, polymer-based nanoparticles are an especially promising tool for clinical translation of combination therapies with tunable dosing schedules. We review polymer nanoparticle (e.g., micelles, dendrimers, and lipid nanoparticles) carriers of drug combinations formulated to treat ovarian cancer. In particular, the focus on this review is combinations of platinum and taxane agents (commonly used first line treatments for ovarian cancer) combined with other small molecule therapeutic agents. In vitro and in vivo drug potency are discussed with a focus on quantifiable synergistic effects. The effect of drug sequence and dosing schedule is examined. Computational approaches as a tool to predict synergistic drug combinations and dosing schedules as a tool for future nanoparticle design are also briefly discussed.
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spelling pubmed-80725322021-04-27 Polymeric Nanoparticle Delivery of Combination Therapy with Synergistic Effects in Ovarian Cancer Levit, Shani L. Tang, Christina Nanomaterials (Basel) Review Treatment of ovarian cancer is challenging due to late stage diagnosis, acquired drug resistance mechanisms, and systemic toxicity of chemotherapeutic agents. Combination chemotherapy has the potential to enhance treatment efficacy by activation of multiple downstream pathways to overcome drug resistance and reducing required dosages. Sequence of delivery and the dosing schedule can further enhance treatment efficacy. Formulation of drug combinations into nanoparticles can further enhance treatment efficacy. Due to their versatility, polymer-based nanoparticles are an especially promising tool for clinical translation of combination therapies with tunable dosing schedules. We review polymer nanoparticle (e.g., micelles, dendrimers, and lipid nanoparticles) carriers of drug combinations formulated to treat ovarian cancer. In particular, the focus on this review is combinations of platinum and taxane agents (commonly used first line treatments for ovarian cancer) combined with other small molecule therapeutic agents. In vitro and in vivo drug potency are discussed with a focus on quantifiable synergistic effects. The effect of drug sequence and dosing schedule is examined. Computational approaches as a tool to predict synergistic drug combinations and dosing schedules as a tool for future nanoparticle design are also briefly discussed. MDPI 2021-04-20 /pmc/articles/PMC8072532/ /pubmed/33923947 http://dx.doi.org/10.3390/nano11041048 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Levit, Shani L.
Tang, Christina
Polymeric Nanoparticle Delivery of Combination Therapy with Synergistic Effects in Ovarian Cancer
title Polymeric Nanoparticle Delivery of Combination Therapy with Synergistic Effects in Ovarian Cancer
title_full Polymeric Nanoparticle Delivery of Combination Therapy with Synergistic Effects in Ovarian Cancer
title_fullStr Polymeric Nanoparticle Delivery of Combination Therapy with Synergistic Effects in Ovarian Cancer
title_full_unstemmed Polymeric Nanoparticle Delivery of Combination Therapy with Synergistic Effects in Ovarian Cancer
title_short Polymeric Nanoparticle Delivery of Combination Therapy with Synergistic Effects in Ovarian Cancer
title_sort polymeric nanoparticle delivery of combination therapy with synergistic effects in ovarian cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072532/
https://www.ncbi.nlm.nih.gov/pubmed/33923947
http://dx.doi.org/10.3390/nano11041048
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