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.
Disclosure statement
The authors declare no competing financial interests and no conflict of interest related to manuscript.
Funding information
The research described in this original paper was supported by grant funding from the Canadian Institutes of Health Research (MOP-102611) and the Canadian Cancer Society Research Institute (Award # 702491).