title: Active loading and tunable release of doxorubicin from block copolymer vesicles.
abstract: Vesicles are spherical bilayers that offer a hydrophilic reservoir, suitable for the incorporation of water-soluble molecules, as well as a hydrophobic wall that protects the loaded molecules from the external solution. The permeability of a vesicle wall made from polystyrene can be enhanced by adding a plasticizer such as dioxane. Tuning the wall permeability allows loading and release of molecules from vesicles to be controlled. In this study, vesicles are prepared from polystyrene(310)-b-poly(acrylic acid)(36) and used as model carriers for doxorubicin (DXR), a weak amine and a widely used anticancer drug. To increase the wall permeability, different amounts of dioxane are added to the vesicle solution. A pH gradient is created across the vesicle wall (inside acidic) and used as an active loading method to concentrate the drug inside the vesicles. The results show that a pH gradient of ca. 3.8 units can enhance the loading level up to 10-fold relative to loading in the absence of the gradient. After loading, the release of DXR from vesicles is followed as a function of the wall permeability. The diffusion coefficient of doxorubicin through polystyrene (D) is evaluated from the initial slope of the release curves; the value of D ranges from 8 x 10(-17) to 6 x 10(-16) cm(2)/s, depending on the degree of plasticization of the vesicle wall.
authors.affiliation: Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quebec, Canada H3A 2K6.
authors.forename: Amira
authors.initials: A
authors.lastname: Choucair
authors.forename: Patrick Lim
authors.initials: PL
authors.lastname: Soo
authors.forename: Adi
authors.initials: A
authors.lastname: Eisenberg
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D004058:Diffusion; D004146:Dioxanes / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008567:Membranes, Artificial; D008689:Methacrylates / Q000737:chemistry*; D010539:Permeability; D010968:Plasticizers / Q000737:chemistry; D011137:Polystyrenes / Q000737:chemistry*; D013997:Time Factors
chemical_list: D000903:Antibiotics, Antineoplastic; D004146:Dioxanes; D008567:Membranes, Artificial; D008689:Methacrylates; D010968:Plasticizers; D011137:Polystyrenes; D004317:Doxorubicin; C025223:1,4-dioxane