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A Bilayer Vaginal Tablet for the Localized Delivery of Disulfiram and 5-Fluorouracil to the Cervix

This study was performed to develop an adjuvant therapy in the form of a self-administered vaginal tablet regimen for the localized delivery of chemotherapeutic drugs. This therapy will help to reduce relapse by eradicating cancerous cells in the margin of cervical tumors. The vaginal tablet is a ve...

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Autores principales: Abidin, Ismin Zainol, Rezoagli, Emanuele, Simonassi-Paiva, Bianca, Fehrenbach, Gustavo Waltzer, Masterson, Kevin, Pogue, Robert, Cao, Zhi, Rowan, Neil, Murphy, Emma J., Major, Ian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762309/
https://www.ncbi.nlm.nih.gov/pubmed/33291349
http://dx.doi.org/10.3390/pharmaceutics12121185
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author Abidin, Ismin Zainol
Rezoagli, Emanuele
Simonassi-Paiva, Bianca
Fehrenbach, Gustavo Waltzer
Masterson, Kevin
Pogue, Robert
Cao, Zhi
Rowan, Neil
Murphy, Emma J.
Major, Ian
author_facet Abidin, Ismin Zainol
Rezoagli, Emanuele
Simonassi-Paiva, Bianca
Fehrenbach, Gustavo Waltzer
Masterson, Kevin
Pogue, Robert
Cao, Zhi
Rowan, Neil
Murphy, Emma J.
Major, Ian
author_sort Abidin, Ismin Zainol
collection PubMed
description This study was performed to develop an adjuvant therapy in the form of a self-administered vaginal tablet regimen for the localized delivery of chemotherapeutic drugs. This therapy will help to reduce relapse by eradicating cancerous cells in the margin of cervical tumors. The vaginal tablet is a very common formulation that is easy to manufacture, easy to place in the vagina, and has a low cost of manufacture, making them ideal for use in developing countries. A combination of disulfiram and 5-fluorouracil, which are both off-patent drugs and provide different modes of action, were evaluated. The tablets developed were evaluated for weight variation, thickness, hardness, friability, swelling index, differential scanning calorimetry (DSC), particle morphology, in vitro drug release, and cytotoxicity on Ca-Ski cells. Both layers were designed to release both drugs concurrently for a synergistic effect. The polymer–polymer interaction between the layers was able to reduce the loss of formulation due to chitosan. While the bilayer tablet had satisfactory performance in the physicochemical tests, in vitro cell culture with Ca-Ski also showed a synergistic effect using a combination of drugs at a low dose. However, the formulation only had 24-h dose release before degradation. Further drug combinations should be evaluated in subsequent studies.
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spelling pubmed-77623092020-12-26 A Bilayer Vaginal Tablet for the Localized Delivery of Disulfiram and 5-Fluorouracil to the Cervix Abidin, Ismin Zainol Rezoagli, Emanuele Simonassi-Paiva, Bianca Fehrenbach, Gustavo Waltzer Masterson, Kevin Pogue, Robert Cao, Zhi Rowan, Neil Murphy, Emma J. Major, Ian Pharmaceutics Article This study was performed to develop an adjuvant therapy in the form of a self-administered vaginal tablet regimen for the localized delivery of chemotherapeutic drugs. This therapy will help to reduce relapse by eradicating cancerous cells in the margin of cervical tumors. The vaginal tablet is a very common formulation that is easy to manufacture, easy to place in the vagina, and has a low cost of manufacture, making them ideal for use in developing countries. A combination of disulfiram and 5-fluorouracil, which are both off-patent drugs and provide different modes of action, were evaluated. The tablets developed were evaluated for weight variation, thickness, hardness, friability, swelling index, differential scanning calorimetry (DSC), particle morphology, in vitro drug release, and cytotoxicity on Ca-Ski cells. Both layers were designed to release both drugs concurrently for a synergistic effect. The polymer–polymer interaction between the layers was able to reduce the loss of formulation due to chitosan. While the bilayer tablet had satisfactory performance in the physicochemical tests, in vitro cell culture with Ca-Ski also showed a synergistic effect using a combination of drugs at a low dose. However, the formulation only had 24-h dose release before degradation. Further drug combinations should be evaluated in subsequent studies. MDPI 2020-12-06 /pmc/articles/PMC7762309/ /pubmed/33291349 http://dx.doi.org/10.3390/pharmaceutics12121185 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Abidin, Ismin Zainol
Rezoagli, Emanuele
Simonassi-Paiva, Bianca
Fehrenbach, Gustavo Waltzer
Masterson, Kevin
Pogue, Robert
Cao, Zhi
Rowan, Neil
Murphy, Emma J.
Major, Ian
A Bilayer Vaginal Tablet for the Localized Delivery of Disulfiram and 5-Fluorouracil to the Cervix
title A Bilayer Vaginal Tablet for the Localized Delivery of Disulfiram and 5-Fluorouracil to the Cervix
title_full A Bilayer Vaginal Tablet for the Localized Delivery of Disulfiram and 5-Fluorouracil to the Cervix
title_fullStr A Bilayer Vaginal Tablet for the Localized Delivery of Disulfiram and 5-Fluorouracil to the Cervix
title_full_unstemmed A Bilayer Vaginal Tablet for the Localized Delivery of Disulfiram and 5-Fluorouracil to the Cervix
title_short A Bilayer Vaginal Tablet for the Localized Delivery of Disulfiram and 5-Fluorouracil to the Cervix
title_sort bilayer vaginal tablet for the localized delivery of disulfiram and 5-fluorouracil to the cervix
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762309/
https://www.ncbi.nlm.nih.gov/pubmed/33291349
http://dx.doi.org/10.3390/pharmaceutics12121185
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