| Autor: |
Yige Fu, Drishti Rathod, Ehab M. Abo-Ali, Vikas V. Dukhande, Ketan Patel |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Pharmaceutics, Vol 11, Iss 10, p 504 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
1999-4923 |
| DOI: |
10.3390/pharmaceutics11100504 |
| Popis: |
The clinical outcomes of malignant melanoma have improved with the introduction of mitogen-activated protein kinase kinase (MEK) inhibitors. However, off-target toxicities of the MEK inhibitor trametinib (TMB) often result in dose interruption and discontinuation of therapy. The purpose of this study was to anchor a physically stable EphrinA1-mimicking peptide known as YSA (YSAYPDSVPMMS) on TMB-loaded PEGylated nanoliposomes (YTPLs), and evaluate them in BRAFV600E-mutated parent cells (lines A375 and SK-MEL-28) and vemurafenib-resistant cells lines (A375R and SK-MEL-28R) in melanoma. TMB-loaded PEGylated liposomes (TPL) functionalized with nickel-chelated phospholipids were prepared using a modified hydration method. The hydrodynamic diameter and zeta potential values of optimized YTPL were 91.20 ± 12.16 nm and –0.92 ± 3.27 mV, respectively. The drug release study showed TPL did not leak or burst release in 24 h. The hemolysis observed was negligible at therapeutic concentrations of TMB. A differential scanning calorimetry (DSC) study confirmed that TMB was retained in a solubilized state within lipid bilayers. YTPL showed higher intracellular uptake in parental cell lines compared to vemurafenib-resistant cell lines. Western blot analysis and a cytotoxicity study with the EphA2 inhibitor confirmed a reduction in EphA2 expression in resistant cell lines. Thus, EphA2 receptor-targeted nanoliposomes can be useful for metastatic melanoma-specific delivery of TMB. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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