TY - JOUR
T1 - Multifunctional LUV liposomes decorated for BBB and amyloid targeting. A. In vitro proof-of-concept
AU - Papadia, Konstantina
AU - Markoutsa, Eleni
AU - Mourtas, Spyridon
AU - Giannou, Anastassios D.
AU - La Ferla, Barabara
AU - Nicotra, Fransesco
AU - Salmona, Mario
AU - Klepetsanis, Pavlos
AU - Stathopoulos, Georgios T.
AU - Antimisiaris, Sophia G.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - Multifunctional LUV liposomes (mf-LIPs) were developed, having a curcumin-lipid ligand (TREG) with affinity towards amyloid species, together with ligands to target the transferrin and the LDL receptors of the blood-brain-barrier (BBB), on their surface. mf-LIPs were evaluated for their brain targeting, on hCMEC/D3 monolayers, and for their ability to inhibit Aβ-peptide aggregation. The transport of mf-LIP across hCMEC/D3 monolayers was similar to that of BBB-LIPs, indicating that the presence of TREG on their surface does not reduce their brain targeting potential. Likewise, mf-LIP inhibitory effect on Aβ aggregation was similar to that of LIPs functionalized only with TREG, proving that the presence of brain targeting ligands does not reduce the functionality of the amyloid-specific ligand. Addition of the curcumin-lipid in some liposome types was found to enhance their integrity and reduce the effect of serum proteins on their interaction with brain endothelial cells. Finally, preliminary in vivo results confirm the in vitro findings. Concluding, the current results reveal the potential of the specific curcumin-lipid derivative as a component of multifunctional LIPs with efficient brain targeting capability, intended to act as a theragnostic system for AD.
AB - Multifunctional LUV liposomes (mf-LIPs) were developed, having a curcumin-lipid ligand (TREG) with affinity towards amyloid species, together with ligands to target the transferrin and the LDL receptors of the blood-brain-barrier (BBB), on their surface. mf-LIPs were evaluated for their brain targeting, on hCMEC/D3 monolayers, and for their ability to inhibit Aβ-peptide aggregation. The transport of mf-LIP across hCMEC/D3 monolayers was similar to that of BBB-LIPs, indicating that the presence of TREG on their surface does not reduce their brain targeting potential. Likewise, mf-LIP inhibitory effect on Aβ aggregation was similar to that of LIPs functionalized only with TREG, proving that the presence of brain targeting ligands does not reduce the functionality of the amyloid-specific ligand. Addition of the curcumin-lipid in some liposome types was found to enhance their integrity and reduce the effect of serum proteins on their interaction with brain endothelial cells. Finally, preliminary in vivo results confirm the in vitro findings. Concluding, the current results reveal the potential of the specific curcumin-lipid derivative as a component of multifunctional LIPs with efficient brain targeting capability, intended to act as a theragnostic system for AD.
KW - Brain
KW - Curcumin
KW - Liposomes
KW - Nanoparticle
KW - Targeting
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UR - http://www.scopus.com/inward/citedby.url?scp=85013115033&partnerID=8YFLogxK
U2 - 10.1016/j.ejps.2017.02.019
DO - 10.1016/j.ejps.2017.02.019
M3 - Article
C2 - 28193538
AN - SCOPUS:85013115033
VL - 101
SP - 140
EP - 148
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
SN - 0928-0987
ER -