title: Evaluation of β-cyclodextrin-modified gemini surfactant-based delivery systems in melanoma models.
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.
authors.affiliation: Drug Design and Discovery Research Group, College of Pharmacy and Nutrition.
authors.forename: Deborah
authors.initials: D
authors.lastname: Michel
authors.affiliation: Drug Design and Discovery Research Group, College of Pharmacy and Nutrition.
authors.forename: Waleed
authors.initials: W
authors.lastname: Mohammed-Saeid
authors.affiliation: Drug Design and Discovery Research Group, College of Pharmacy and Nutrition.
authors.forename: Heather
authors.initials: H
authors.lastname: Getson
authors.affiliation: Drug Design and Discovery Research Group, College of Pharmacy and Nutrition.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Roy
authors.affiliation: Drug Design and Discovery Research Group, College of Pharmacy and Nutrition.
authors.forename: Masoomeh
authors.initials: M
authors.lastname: Poorghorban
authors.affiliation: Department of Chemistry, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Jackson M
authors.initials: JM
authors.lastname: Chitanda
authors.affiliation: Department of Chemistry, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Ronald
authors.initials: R
authors.lastname: Verrall
authors.affiliation: Drug Design and Discovery Research Group, College of Pharmacy and Nutrition.
authors.forename: Ildiko
authors.initials: I
authors.lastname: Badea
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000737:chemistry; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008558:Melphalan / Q000008:administration & dosage / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D010316:Particle Size; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000644:Quaternary Ammonium Compounds; D013501:Surface-Active Agents; D047392:beta-Cyclodextrins; C576934:mono-6-O-(3-(bis(3-(N-dodecyl-N,N-dimethylamino)propyl)carbamoyl)propanoyl)-beta-cyclodextrin; D008558:Melphalan
keywords: anticancer agent; apoptosis; drug resistance; flow cytometry; lipid nanoparticles; spheroid; zeta potential