Transport of nerve growth factor encapsulated into liposomes across the blood-brain barrier: in vitro and in vivo studies.
A nerve growth factor (NGF) was encapsulated into liposomes in order to protect it from the enzyme degradation in vivo and promote it permeability across the blood-brain barrier (BBB). RMP-7, a ligand to the B2 receptor on brain microvascular endothelial cells (BMVEC), was combined with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-n-[poly(ethylenegly-col)]-hydroxy succinamide (DSPE-PEG-NHS) to obtain DSPE-PEG-RMP-7. Then DSPE-PEG-RMP-7 was incorporated into the liposomes' surface to target sterically stabilized liposomes (SSL-T) to the brain. The highest percent of NGF encapsulated into liposomes was about 34%, and the average size of liposomes was below 100 nm. A primary model of BBB was established and evaluated by morphological, permeability, and transendothelial electrical resistance (TEER). The BBB model was employed to study the permeability of NGF liposomes in vitro. The results indicated that the liposomes could enhance transport of NGF across the BBB. The best transport rate was received with NGF-SSL-T. The brain distribution of NGF liposomes was studied in vivo, the amount of NGF in the brain was increased in the order: NGF-SSL-T>NGF-SSL+RMP-7>NGF-SSL>NGF-L. The maximum concentration of NGF was recorded in 30 min following the intravenous injection. In particular, a majority of NGF was distributed in striatum, hippocampus and cortex, and the concentration of NGF was relatively lower in olfactory bulb, cerebellum and brain stem. There was a close relationship between P(e) (permeability coefficient on in vitro BBB model) and T(e) (brain targeted coefficient in vivo) for NGF encapsulated into the liposomes.
Xie
Ying
Y
Department of Physical Pharmacy, School of Pharmaceutical Science, Xueyuan Road #38, Peking University, Beijing 100083, PR China.
Ye
Liya
L
Zhang
Xiaobin
X
Cui
Wei
W
Lou
Jinning
J
Nagai
Tsuneji
T
Hou
Xinpu
X
D000818:Animals; D001693:Biological Transport, Active; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002463:Cell Membrane Permeability; D004337:Drug Carriers; D004553:Electric Conductivity; D004591:Electrophoresis, Polyacrylamide Gel; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D007457:Iodine Radioisotopes; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D009414:Nerve Growth Factors / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D004337:Drug Carriers; D005456:Fluorescent Dyes; D007457:Iodine Radioisotopes; D008081:Liposomes; D009414:Nerve Growth Factors; D016650:Fluorescein-5-isothiocyanate