Role of the complement cascade in the biological fate of liposomes in rodents. Issue 36 (9th September 2020)

• Record Type: Journal Article
• Authors: Viana, Iara Maíra de Oliveira; Grenier, Philippe; Defrêne, Joan; Barabé, Frédéric; Lima, Eliana Martins; Bertrand, Nicolas
• Is Part Of: Nanoscale. Volume 12:Issue 36(2020)
• Page Start: 18875
• Page End: 18884
• Publication Date: 2020-09-09
• Subjects: Nanoscience -- Periodicals; Nanotechnology -- Periodicals; 620.505
• DOI: 10.1039/d0nr04100a
• Languages: English
• ISSNs: 2040-3364

Abstract

Abstract : The complement cascade plays a minor role in the circulation kinetics of liposomes but affects their distribution to splenic cells. Abstract : Nanomedicines, including liposomes, have been used to improve the clinical efficacy and safety of drugs. In some liposomal formulations, a hydrophilic polymer coating of poly(ethylene glycol) (PEG) is used to increase the circulation time. Understanding the biological mechanisms responsible for the clearance of PEGylated and non-PEGylated nanomedicines is necessary to develop better-performing materials. The purpose of this work is to explore the role of complement in the elimination of intravenously administered liposomes (PEGylated and non-PEGylated) in mice and rats. Here, the complement cascade was depleted by intraperitoneal injections of cobra venom factor (CVF) 12 and 24 hours before the intravenous injection of radiolabeled liposomes. In both mice and rats, non-PEGylated liposomes showed faster elimination than PEGylated liposomes. At a lipid dose of 20 mg kg −1, the abrogation of the complement cascade (in CVF group) did not alter the circulation time of either PEGylated or non-PEGylated liposomes. In contrast, at lower doses (2 mg kg −1 ), animals treated with CVF had slightly higher levels of circulating liposomes, especially during the 24 hours pharmacokinetic studies. The complement cascade seems to govern the uptake of non-PEGylated liposomes by splenic B cells. Altogether, these results suggest that although PEGylated and non-PEGylated liposomes can activate complement, the impact of this cascade on their circulation time is minor and mostly perceivable at later phases of distribution. This work enlightens biological pathways responsible for in vivo clearance of liposomes and will help in orienting future research in elucidating the nano-bio interface.