Evaluation of β-cyclodextrin-modified gemini surfactant-based delivery systems in melanoma models
| Autor: | Waleed Mohammed-Saeid, Heather M Getson, Deborah Michel, Ronald E. Verrall, Caitlin Roy, Masoomeh Poorghorban, Jackson M. Chitanda, Ildiko Badea |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Melphalan
Pharmaceutical Science 02 engineering and technology Drug resistance lipid nanoparticles 01 natural sciences Drug Delivery Systems International Journal of Nanomedicine hemic and lymphatic diseases Drug Discovery Melanoma Original Research media_common Cell Death Chemistry beta-Cyclodextrins apoptosis General Medicine 021001 nanoscience & nanotechnology Drug delivery 0210 nano-technology medicine.drug Drug media_common.quotation_subject Biophysics Bioengineering Endocytosis Biomaterials Inhibitory Concentration 50 Surface-Active Agents zeta potential Cell Line Tumor medicine Humans Particle Size Antineoplastic Agents Alkylating neoplasms IC50 drug resistance flow cytometry 010401 analytical chemistry Organic Chemistry medicine.disease anticancer agent 0104 chemical sciences Quaternary Ammonium Compounds Solubility Drug Resistance Neoplasm spheroid Apoptosis Cancer research Nanoparticles |
| Zdroj: | International Journal of Nanomedicine |
| ISSN: | 1178-2013 |
| DOI: | 10.2147/ijn.s121156 |
| Popis: | Deborah Michel,1 Waleed Mohammed-Saeid,1 Heather Getson,1 Caitlin Roy,1 Masoomeh Poorghorban,1 Jackson M Chitanda,2 Ronald Verrall,2 Ildiko Badea1 1Drug Design and Discovery Research Group, College of Pharmacy and Nutrition, 2Department of Chemistry, University of Saskatchewan, Saskatoon, SK, Canada Abstract: Novel drug delivery systems are developed to improve the biological behavior of poorly soluble drugs and to improve therapeutic outcomes. In melanoma therapy, the goal is efficient drug delivery and mitigation of drug resistance. Melphalan (Mel), a currently used therapeutic agent for melanoma, requires solvent system for solubilization, leading to poor chemical stability. Moreover, drug resistance often renders the drug inefficient in clinical setting. A novel β-cyclodextrin-modified gemini surfactant (CDgemini) delivery system was developed to incorporate Mel in order to improve its physicochemical and biological behavior. Melphalan nanoparticles (Mel-NP) showed optimal particle size in the 200–250 nm range for endocytosis and induced significantly higher cell death compared with Mel (50% of inhibitory concentration [IC50]of 36 µM for the complexes vs 82 µM for Mel). The CDgemini delivery system did not alter the pathway of the cellular death triggered by Mel and caused no intrinsic toxicity to the cells. The Mel-NP complexes induced significant cell death in melanoma cells that were rendered resistant to Mel. These findings demonstrate in principle the applicability of the CDgemini delivery system as safe and efficient alternative to the current melanoma therapy, especially in chemoresistant cases. Keywords: lipid nanoparticles, anticancer agent, drug resistance, apoptosis, spheroid, zeta potential, flow cytometry |
| Databáze: | OpenAIRE |
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