TY - JOUR
T1 - Cationic liposomes target sites of acute neuroinflammation in experimental autoimmune encephalomyelitis
AU - Cavaletti, Guido
AU - Cassetti, Arianna
AU - Canta, Annalisa
AU - Galbiati, Stefania
AU - Gilardini, Alessandra
AU - Oggioni, Norberto
AU - Rodriguez-Menendez, Virginia
AU - Fasano, Anna
AU - Liuzzi, Grazia Maria
AU - Fattler, Ursula
AU - Ries, Stefan
AU - Nieland, John
AU - Riccio, Paolo
AU - Haas, Heinrich
PY - 2009/10/5
Y1 - 2009/10/5
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Blood-brain barrier, BBB
KW - Cancer
KW - Cationic liposomes
KW - Drug delivery
KW - Experimental autoimmune encephalomyelitis, EAE
KW - Inflammation
KW - Multiple sclerosis, MS
UR - http://www.scopus.com/inward/record.url?scp=68049091042&partnerID=8YFLogxK
U2 - 10.1021/mp8001478
DO - 10.1021/mp8001478
M3 - Journal article
C2 - 19281192
AN - SCOPUS:68049091042
SN - 1543-8384
VL - 6
SP - 1363
EP - 1370
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
IS - 5
ER -