Cationic liposomes target sites of acute neuroinflammation in experimental autoimmune encephalomyelitis

Guido Cavaletti, Arianna Cassetti, Annalisa Canta, Stefania Galbiati, Alessandra Gilardini, Norberto Oggioni, Virginia Rodriguez-Menendez, Anna Fasano, Grazia Maria Liuzzi, Ursula Fattler, Stefan Ries, John Nieland, Paolo Riccio, Heinrich Haas*

*Kontaktforfatter

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

28 Citationer (Scopus)

Abstract

The binding selectivity of charged liposomes to the spinal cord of rats affected by experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, was investigated. Positively and negatively charged liposomes were injected into the tail vein of rats, and blood/brain barrier (BBB) targeting was determined by confocal microscopy as a function of the temporal evolution of the inflammatory response. Accumulation in spinal cord endoneural vessels was observed for cationic, but not for anionic, liposomes, and only in EAE but not in healthy rats. The overall binding efficacy paralleled the severity of the clinical score, but targeting was observed already before clinical manifestation of inflammation. Preferential binding of positively charged liposomes in the course of acute EAE can be ascribed to subtle changes of BBB morphology and charge distribution in a similar way as for the binding of cationic particles to proliferating vasculature in chronic inflammation and angiogenesis. Our findings suggest that vascular changes related to increased binding affinity for cationic particles are very early events within the inflammatory reaction in acute EAE. Investigation of cationic vascular targeting can help to shed further light on these occurrences, and, potentially, new diagnostic and therapeutic options may become available. In neuroinflammatory diseases, cationic colloidal carrier particles may enable intervention at affected BBB by an approach which is independent from permeability increase.

OriginalsprogEngelsk
TidsskriftMolecular Pharmaceutics
Vol/bind6
Udgave nummer5
Sider (fra-til)1363-1370
Antal sider8
ISSN1543-8384
DOI
StatusUdgivet - 5 okt. 2009
Udgivet eksterntJa

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