Cationic liposomes target sites of acute neuroinflammation in experimental autoimmune encephalomyelitis.
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.
Cavaletti
Guido
G
Department of Neurosciences, University of Milan "Bicocca", 20052 Monza, Italy.
Cassetti
Arianna
A
Canta
Annalisa
A
Galbiati
Stefania
S
Gilardini
Alessandra
A
Oggioni
Norberto
N
Rodriguez-Menendez
Virginia
V
Fasano
Anna
A
Liuzzi
Grazia Maria
GM
Fattler
Ursula
U
Ries
Stefan
S
Nieland
John
J
Riccio
Paolo
P
Haas
Heinrich
H
D000818:Animals; D001812:Blood-Brain Barrier; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry*; D018613:Microscopy, Confocal; D009389:Neovascularization, Pathologic; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D055672:Static Electricity
D004337:Drug Carriers; D008081:Liposomes