title: PRCosomes: pretty reactive complexes formed in liposomes.
abstract: As a tribute to Pieter R. Cullis, this manuscript identifies a liposomal formulation that bears his initials: the PRCosomes. "Pretty" Reactive Complexes within liposomes were observed, while the senior author of this manuscript completed his Ph.D. thesis under Pieter's supervision. The dye (safranine) was used as a tool to measure the magnitude of the transmembrane gradient generated with liposomes. The dye's redistribution is easily detected by eye and correlates with >98% encapsulation of the dye. This observation became the basis from which remote drug loading methods developed. Remote loading methodology involves the addition of drugs to pre-formed liposomes with a transmembrane gradient, which results in drug redistribution to the liposome interior. Doxorubicin, as an example drug candidate, complexes manganese trapped within the liposome. A color change accompanied drug encapsulation as the solution went from an orange to purple. This manuscript reviews and adds a novel perspective on the use of metal complexation reactions to prepare PRCosomes. The technology described provides a versatile method to form metal-drug complexed within liposomes. The purpose of this work is to differentiation between drug candidate loading that is caused by metal-drug complexation and loading driven by formation of a pH gradient.
authors.affiliation: a Experimental Therapeutics, British Columbia Cancer Agency , Vancouver , BC , Canada.|b Faculty of Pharmaceutical Sciences , University of British Columbia , Vancouver , BC , Canada.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Wehbe
authors.affiliation: a Experimental Therapeutics, British Columbia Cancer Agency , Vancouver , BC , Canada.|c Department of Pathology and Laboratory Medicine , University of British Columbia , Vancouver , BC , Canada.
authors.forename: Lina
authors.initials: L
authors.lastname: Chernov
authors.affiliation: a Experimental Therapeutics, British Columbia Cancer Agency , Vancouver , BC , Canada.|d Department of Interdisciplinary Oncology , BC Cancer Research Centre , Vancouver , BC , Canada.
authors.forename: Kent
authors.initials: K
authors.lastname: Chen
authors.affiliation: a Experimental Therapeutics, British Columbia Cancer Agency , Vancouver , BC , Canada.|b Faculty of Pharmaceutical Sciences , University of British Columbia , Vancouver , BC , Canada.|c Department of Pathology and Laboratory Medicine , University of British Columbia , Vancouver , BC , Canada.|d Department of Interdisciplinary Oncology , BC Cancer Research Centre , Vancouver , BC , Canada.|e Center for Drug Research and Development , Vancouver , BC , Canada.
authors.forename: Marcel B
authors.initials: MB
authors.lastname: Bally
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry*; D016503:Drug Delivery Systems; D008081:Liposomes / Q000737:chemistry*; D008563:Membrane Lipids; D008670:Metals / Q000737:chemistry*
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D008563:Membrane Lipids; D008670:Metals; D004317:Doxorubicin
keywords: Copper; drug loading; liposome; manganese; metal-complexation; pH gradient