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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...

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Autores principales: Mishra, Harshita, Mishra, Pawan Kumar, Iqbal, Zeenat, Jaggi, Manu, Madaan, Alka, Bhuyan, Kimi, Gupta, Namita, Gupta, Neha, Vats, Karnika, Verma, Ritu, Talegaonkar, Sushama
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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