Immunocompatibility of Rad-PC-Rad liposomes in vitro, based on human complement activation and cytokine release

Matviykiv, S. et al. (2018) Immunocompatibility of Rad-PC-Rad liposomes in vitro, based on human complement activation and cytokine release. Precision Nanomedicine, 1(1), pp. 43-62. (doi: 10.29016/180419.2)

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Liposomal drug delivery systems can protect pharmaceutical substances and control their release. Systemic administration of liposomes, however, often activate the innate immune system, resulting in hypersensitivity reactions. These pseudo-allergic reactions can be interpreted as activating the complement system. Complement activation destroys and eliminates foreign substances, either directly through opsonization and the formation of the membrane attack complex (MAC), or by activating leukocytes and initiating inflammatory responses via mediators, such as cytokines. In this study, we investigated the in vitro immune toxicity of the recently synthesized Rad-PC- Rad liposomes, analyzing the liposome-induced complement activation. In five human sera, Rad-PC-Rad liposomes did not induce activation, but in one serum high sensitivity via alternative pathway was detected. Such a behavior in adverse phenomena is characteristic for patient-to-patient variation and, thus, the number of donors should be in the order of hundreds rather than tens – hence the present study based on six donors has preliminary character. In order to further prove the suitability of mechano-responsive Rad-PC-Rad liposomes for clinical trials, the production of pro-inflammatory cytokines was examined by human white blood cells. The concentrations of the pro-inflammatory cytokines, IL-6, IL-12p70, TNF-α, and IL-1β, induced by Rad-PC-Rad liposomal formulations, incubated with whole blood samples, were smaller or comparable to saline (negative control). Because of this favorable in vitro hemo- compatibility, in vivo investigations using these mechano-responsive liposomes should be designed.

Item Type:Articles
Keywords:Nanomedicines, non-spherical liposomes, immune toxicity, complement activation, hypersensitivity reactions, pro-inflammatory cytokines.
Glasgow Author(s) Enlighten ID:Gerganova, Gabriela
Authors: Matviykiv, S., Buscema, M., Gerganova, G., Mészáros, T., Kozma, G., Mettal, U., Neuhaus, F., Ishikawa, T., Szebeni, J., Zumbuehl, A., and Müller, B.
Subjects:Q Science > Q Science (General)
Q Science > QC Physics
Q Science > QP Physiology
R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences
Journal Name:Precision Nanomedicine
Publisher:Andover House
ISSN (Online):2639-9431
Published Online:19 April 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Precision Nanomedicine 1(1) 43-62
Publisher Policy:Reproduced under a Creative Commons License

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