caa a22 4500 445313315 CHVBK 20180317142637.0 cr unu---uuuuu 170323e20110401xx s 000 0 eng 10.1007/s11095-010-0340-2 doi (NATIONALLICENCE)springer-10.1007/s11095-010-0340-2 The Role of the Transition Metal Copper and the Ionophore A23187 in the Development of Irinophore C™ [Elektronische Daten] [Nilesh Patankar, Malathi Anantha, Euan Ramsay, Dawn Waterhouse, Marcel Bally] ABSTRACT: Purpose: A liposomal irinotecan formulation referred to as Irinophore C relies on the ability of copper to complex irinotecan within the liposome. It is currently being evaluated for critical drug-loading parameters. Studies presented here were designed to determine the optimum copper concentration required for the effective encapsulation and retention of irinotecan into liposomes. Methods: Distearoylphosphatidylcholine/cholesterol liposomes were formulated using buffers containing various copper or manganese concentrations, and irinotecan loading was determined in the presence and absence of divalent metal ionophore A23187. The rate and extent of irinotecan encapsulation and the rate of irinotecan release from the liposomes were assessed. The amount of copper retained inside liposomes following irinotecan loading and the effect of copper on membrane permeability were determined. Results: Efficient (>98%) irinotecan loading was achieved using encapsulated copper concentrations of 50mM. However, irinotecan release was copper concentration dependent, with a minimum 300mM concentration required for optimal drug retention. The presence of copper increased liposomal membrane permeability. Conclusion: Results explain why irinotecan loading rates are enhanced in the presence of formulations prepared with copper, and we speculate that the Irinophore C formulation exhibits improved drug retention, due to generation of a complex between copper and irinotecan. Springer Science+Business Media, LLC, 2010 copper nationallicence ionophore nationallicence irinotecan nationallicence liposomes nationallicence Patankar Nilesh Faculty of Pharmaceutical Sciences, University of British Columbia, V6T1Z3, Vancouver, British Columbia, Canada aut Anantha Malathi Experimental Therapeutics, B C Cancer Agency, 675 W 10th Avenue, V5Z 1L3, Vancouver, British Columbia, Canada aut Ramsay Euan Experimental Therapeutics, B C Cancer Agency, 675 W 10th Avenue, V5Z 1L3, Vancouver, British Columbia, Canada aut Waterhouse Dawn Faculty of Pharmaceutical Sciences, University of British Columbia, V6T1Z3, Vancouver, British Columbia, Canada aut Bally Marcel Faculty of Pharmaceutical Sciences, University of British Columbia, V6T1Z3, Vancouver, British Columbia, Canada aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/4(2011-04-01), 848-857 0724-8741 28:4<848 2011 28 11095 https://doi.org/10.1007/s11095-010-0340-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0340-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Patankar Nilesh Faculty of Pharmaceutical Sciences, University of British Columbia, V6T1Z3, Vancouver, British Columbia, Canada aut NATIONALLICENCE 700 1- Anantha Malathi Experimental Therapeutics, B C Cancer Agency, 675 W 10th Avenue, V5Z 1L3, Vancouver, British Columbia, Canada aut NATIONALLICENCE 700 1- Ramsay Euan Experimental Therapeutics, B C Cancer Agency, 675 W 10th Avenue, V5Z 1L3, Vancouver, British Columbia, Canada aut NATIONALLICENCE 700 1- Waterhouse Dawn Faculty of Pharmaceutical Sciences, University of British Columbia, V6T1Z3, Vancouver, British Columbia, Canada aut NATIONALLICENCE 700 1- Bally Marcel Faculty of Pharmaceutical Sciences, University of British Columbia, V6T1Z3, Vancouver, British Columbia, Canada aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/4(2011-04-01), 848-857 0724-8741 28:4<848 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer