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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MDPI AG
2019-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/11/4/163 |
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| author | Harshita Mishra Pawan Kumar Mishra Zeenat Iqbal Manu Jaggi Alka Madaan Kimi Bhuyan Namita Gupta Neha Gupta Karnika Vats Ritu Verma Sushama Talegaonkar |
| author_facet | Harshita Mishra Pawan Kumar Mishra Zeenat Iqbal Manu Jaggi Alka Madaan Kimi Bhuyan Namita Gupta Neha Gupta Karnika Vats Ritu Verma Sushama Talegaonkar |
| author_sort | Harshita Mishra |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T11:01:12Z |
| format | Article |
| id | doaj.art-af17face26e14a0a9ee0885580ad5007 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T11:01:12Z |
| publishDate | 2019-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-af17face26e14a0a9ee0885580ad50072022-12-22T04:28:37ZengMDPI AGPharmaceutics1999-49232019-04-0111416310.3390/pharmaceutics11040163pharmaceutics11040163Co-Delivery of Eugenol and Dacarbazine by Hyaluronic Acid-Coated Liposomes for Targeted Inhibition of Survivin in Treatment of Resistant Metastatic MelanomaHarshita Mishra0Pawan Kumar Mishra1Zeenat Iqbal2Manu Jaggi3Alka Madaan4Kimi Bhuyan5Namita Gupta6Neha Gupta7Karnika Vats8Ritu Verma9Sushama Talegaonkar10Departmant of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, IndiaDepartment of Wood Processing, Mendel University in Brno, 61300 Brno, Czech RepublicDepartmant of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, IndiaDabur Research Foundation, Ghaziabad 201010, IndiaDabur Research Foundation, Ghaziabad 201010, IndiaDabur Research Foundation, Ghaziabad 201010, IndiaDabur Research Foundation, Ghaziabad 201010, IndiaDabur Research Foundation, Ghaziabad 201010, IndiaDabur Research Foundation, Ghaziabad 201010, IndiaDabur Research Foundation, Ghaziabad 201010, IndiaDepartmant of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, IndiaWhile 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.https://www.mdpi.com/1999-4923/11/4/163Quality by Design (QbD)liposomeshyaluronic acidmelanoma treatmentsurvivin inhibitioncytotoxicityapoptosismigration inhibition |
| spellingShingle | Harshita Mishra Pawan Kumar Mishra Zeenat Iqbal Manu Jaggi Alka Madaan Kimi Bhuyan Namita Gupta Neha Gupta Karnika Vats Ritu Verma Sushama Talegaonkar Co-Delivery of Eugenol and Dacarbazine by Hyaluronic Acid-Coated Liposomes for Targeted Inhibition of Survivin in Treatment of Resistant Metastatic Melanoma Pharmaceutics Quality by Design (QbD) liposomes hyaluronic acid melanoma treatment survivin inhibition cytotoxicity apoptosis migration inhibition |
| 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 | Quality by Design (QbD) liposomes hyaluronic acid melanoma treatment survivin inhibition cytotoxicity apoptosis migration inhibition |
| url | https://www.mdpi.com/1999-4923/11/4/163 |
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