Co-Delivery of Eugenol and Dacarbazine by Hyaluronic Acid-Coated Liposomes for Targeted Inhibition of Survivin in Treatment of Resistant Metastatic Melanoma

Pharmaceutics

Ritu Verma¹  Namita Gupta¹  Manu Jaggi¹  Alka Madaan¹  Kimi Bhuyan¹  Karnika Vats¹  Neha Gupta¹  Zeenat Iqbal²  Sushama Talegaonkar²  Harshita Mishra²  PawanKumar Mishra³ 

[1] Dabur Research Foundation, Ghaziabad 201010, India;Departmant of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India;Department of Wood Processing, Mendel University in Brno, 61300 Brno, Czech Republic;

关键词: Quality by Design (QbD);    liposomes;    hyaluronic acid;    melanoma treatment;    survivin inhibition;    cytotoxicity;    apoptosis;    migration inhibition;   

DOI  :  10.3390/pharmaceutics11040163

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown