title: Design and evaluation of cyclodextrin-based delivery systems to incorporate poorly soluble curcumin analogs for the treatment of melanoma.
abstract: Various analogs of curcumin show high in vitro cytotoxic activity and are potential candidates for treating a deadly skin disease, melanoma. Due to the low solubility of the drugs, a new delivery agent, namely a cationic gemini surfactant-conjugated β-cyclodextrin, was designed to incorporate novel drug candidates of the 1,5-diaryl-3-oxo-1,4-pentadienyl family. Based on physicochemical parameters, such as particle size and zeta potential, a schematic model for the potential interaction of the drug with the delivery agent was developed. The drug formulations were highly efficient in inhibiting the growth of melanoma cells, with IC(50) values significantly lower than melphalan, the drug currently used for the treatment of in-transit melanoma. CDgemini formulations showed excellent cellular selectivity, triggering apoptosis in the A375 cell line while showing no cytotoxicity to healthy human epidermal keratinocytes. The goal is to develop this novel nanoparticle approach into a non-invasive therapy for in-transit melanoma metastasis that lacks adequate treatment to date.
authors.affiliation: Drug Design and Discovery Research Group, University of Saskatchewan, Saskatoon, Canada.
authors.forename: Deborah
authors.initials: D
authors.lastname: Michel
authors.forename: Jackson M
authors.initials: JM
authors.lastname: Chitanda
authors.forename: Réka
authors.initials: R
authors.lastname: Balogh
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.forename: Jagbir
authors.initials: J
authors.lastname: Singh
authors.forename: Umashankar
authors.initials: U
authors.lastname: Das
authors.forename: Anas
authors.initials: A
authors.lastname: El-Aneed
authors.forename: Jonathan
authors.initials: J
authors.lastname: Dimmock
authors.forename: Ronald
authors.initials: R
authors.lastname: Verrall
authors.forename: Ildiko
authors.initials: I
authors.lastname: Badea
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D053758:Nanoparticles; D010316:Particle Size; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D000644:Quaternary Ammonium Compounds; D047392:beta-Cyclodextrins; C576934:mono-6-O-(3-(bis(3-(N-dodecyl-N,N-dimethylamino)propyl)carbamoyl)propanoyl)-beta-cyclodextrin; D003474:Curcumin