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Co-Delivery of Eugenol and Dacarbazine by Hyaluronic Acid-Coated Liposomes for Targeted Inhibition of Survivin in Treatment of Resistant Metastatic Melanoma
While melanoma remains a challenge for oncologists, possibilities are being continuously explored to fight resistant metastatic melanoma more effectively. Eugenol is reported to inhibit survivin protein in breast cancer cells. Survivin is also overexpressed by melanoma cells, and is known to impart...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523131/ https://www.ncbi.nlm.nih.gov/pubmed/30987266 http://dx.doi.org/10.3390/pharmaceutics11040163 |
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author | Mishra, Harshita Mishra, Pawan Kumar Iqbal, Zeenat Jaggi, Manu Madaan, Alka Bhuyan, Kimi Gupta, Namita Gupta, Neha Vats, Karnika Verma, Ritu Talegaonkar, Sushama |
author_facet | Mishra, Harshita Mishra, Pawan Kumar Iqbal, Zeenat Jaggi, Manu Madaan, Alka Bhuyan, Kimi Gupta, Namita Gupta, Neha Vats, Karnika Verma, Ritu Talegaonkar, Sushama |
author_sort | Mishra, Harshita |
collection | PubMed |
description | While melanoma remains a challenge for oncologists, possibilities are being continuously explored to fight resistant metastatic melanoma more effectively. Eugenol is reported to inhibit survivin protein in breast cancer cells. Survivin is also overexpressed by melanoma cells, and is known to impart resistance to them against chemotherapy-induced apoptosis. To be able to fight resistant melanoma, we formulated hyaluronic acid (HA)-coated liposomes loaded with an effective combination of anti-melanoma agents (Dacarbazine and Eugenol), using a solvent injection method. Quality-by-Design (QbD) was applied to optimize and obtain a final formulation with the desired quality attributes, and within an acceptable size range. The optimized formulation was then subjected to performance analysis in cell lines. Coated-Dacarbazine Eugenol Liposomes were found to possess 95.08% cytotoxicity at a dacarbazine concentration of 0.5 µg/mL, while Dacarbazine Solution showed only 10.20% cytotoxicity at the same concentration. The number of late apoptotic cells was also found to be much higher (45.16% vs. 8.43%). Furthermore, migration assay and proliferation study also revealed significantly higher inhibition of cell migration and proliferation by Coated-Dacarbazine Eugenol Liposomes, signifying its potential against metastasis. Thus, surface-functionalized dacarbazine- and eugenol-loaded liposomes hold great promise against resistant and aggressive metastatic melanoma, with much less unwanted cytotoxicity and reduced doses of the chemotherapeutic agent. |
format | Online Article Text |
id | pubmed-6523131 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-65231312019-06-04 Co-Delivery of Eugenol and Dacarbazine by Hyaluronic Acid-Coated Liposomes for Targeted Inhibition of Survivin in Treatment of Resistant Metastatic Melanoma Mishra, Harshita Mishra, Pawan Kumar Iqbal, Zeenat Jaggi, Manu Madaan, Alka Bhuyan, Kimi Gupta, Namita Gupta, Neha Vats, Karnika Verma, Ritu Talegaonkar, Sushama Pharmaceutics Article While melanoma remains a challenge for oncologists, possibilities are being continuously explored to fight resistant metastatic melanoma more effectively. Eugenol is reported to inhibit survivin protein in breast cancer cells. Survivin is also overexpressed by melanoma cells, and is known to impart resistance to them against chemotherapy-induced apoptosis. To be able to fight resistant melanoma, we formulated hyaluronic acid (HA)-coated liposomes loaded with an effective combination of anti-melanoma agents (Dacarbazine and Eugenol), using a solvent injection method. Quality-by-Design (QbD) was applied to optimize and obtain a final formulation with the desired quality attributes, and within an acceptable size range. The optimized formulation was then subjected to performance analysis in cell lines. Coated-Dacarbazine Eugenol Liposomes were found to possess 95.08% cytotoxicity at a dacarbazine concentration of 0.5 µg/mL, while Dacarbazine Solution showed only 10.20% cytotoxicity at the same concentration. The number of late apoptotic cells was also found to be much higher (45.16% vs. 8.43%). Furthermore, migration assay and proliferation study also revealed significantly higher inhibition of cell migration and proliferation by Coated-Dacarbazine Eugenol Liposomes, signifying its potential against metastasis. Thus, surface-functionalized dacarbazine- and eugenol-loaded liposomes hold great promise against resistant and aggressive metastatic melanoma, with much less unwanted cytotoxicity and reduced doses of the chemotherapeutic agent. MDPI 2019-04-03 /pmc/articles/PMC6523131/ /pubmed/30987266 http://dx.doi.org/10.3390/pharmaceutics11040163 Text en © 2019 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 Mishra, Harshita Mishra, Pawan Kumar Iqbal, Zeenat Jaggi, Manu Madaan, Alka Bhuyan, Kimi Gupta, Namita Gupta, Neha Vats, Karnika Verma, Ritu Talegaonkar, Sushama Co-Delivery of Eugenol and Dacarbazine by Hyaluronic Acid-Coated Liposomes for Targeted Inhibition of Survivin in Treatment of Resistant Metastatic Melanoma |
title | Co-Delivery of Eugenol and Dacarbazine by Hyaluronic Acid-Coated Liposomes for Targeted Inhibition of Survivin in Treatment of Resistant Metastatic Melanoma |
title_full | Co-Delivery of Eugenol and Dacarbazine by Hyaluronic Acid-Coated Liposomes for Targeted Inhibition of Survivin in Treatment of Resistant Metastatic Melanoma |
title_fullStr | Co-Delivery of Eugenol and Dacarbazine by Hyaluronic Acid-Coated Liposomes for Targeted Inhibition of Survivin in Treatment of Resistant Metastatic Melanoma |
title_full_unstemmed | Co-Delivery of Eugenol and Dacarbazine by Hyaluronic Acid-Coated Liposomes for Targeted Inhibition of Survivin in Treatment of Resistant Metastatic Melanoma |
title_short | Co-Delivery of Eugenol and Dacarbazine by Hyaluronic Acid-Coated Liposomes for Targeted Inhibition of Survivin in Treatment of Resistant Metastatic Melanoma |
title_sort | co-delivery of eugenol and dacarbazine by hyaluronic acid-coated liposomes for targeted inhibition of survivin in treatment of resistant metastatic melanoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523131/ https://www.ncbi.nlm.nih.gov/pubmed/30987266 http://dx.doi.org/10.3390/pharmaceutics11040163 |
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