The brain targeting efficiency following nasally applied MPEG-PLA nanoparticles in rats.
The aim of this study was to encapsulate nimodipine (NM) within methoxy poly(ethylene glycol)-poly(lactic acid) (MPEG-PLA) nanoparticles and to investigate its brain targeting efficiency following intranasal administration. NM-loaded nanoparticles, prepared through an emulsion/solvent evaporation technique, were characterized in terms of size, zeta potential, NM loading and in vitro release. The nanoparticles were administered intranasally to rats, and the concentrations of NM in blood, cerebrospinal fluid (CSF) and brain tissues were monitored. The contribution of the olfactory pathway to the uptake of NM in the brain was determined by calculating the brain/plasma concentration ratios and "brain drug direct transport percentage (DTP)" following intranasal administration of the nanoparticles and the solution formulation. The results showed that MPEG-PLA nanoparticles had a mean particle size of 76.5 +/- 7.4 nm, a negative surface charge and a 5.2% NM loading. In vitro release was moderate under sink conditions. The intranasal administration of nanoparticles resulted in a low but constant NM level in plasma. The ratio of AUC values of the nanoparticles to the solution was 1.56 in CSF. The olfactory bulb/plasma and CSF/plasma concentration ratios were significantly higher (P < 0.05) after application of nanoparticles than those of the nasal solution, except the ratio in olfactory bulb at 5 min. Furthermore, nasally administered nanoparticles yielded 1.6-3.3-fold greater DTP values in CSF, olfactory bulb and other brain tissues compared to nasal solution. Thus, MPEG-PLA nanoparticles demonstrated its potential on improving the efficacy of the direct nose-brain transport for drugs.
Zhang
Qi-Zhi
QZ
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 200032, People's Republic of China.
Zha
Liu-Sheng
LS
Zhang
Yan
Y
Jiang
Wen-Ming
WM
Lu
Wei
W
Shi
Zhen-Qi
ZQ
Jiang
Xin-Guo
XG
Fu
Shou-Kuan
SK
D000281:Administration, Intranasal; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D008297:Male; D049329:Nanostructures; D009553:Nimodipine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011091:Polyesters / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D011091:Polyesters; C492425:methoxy poly(ethylene glycol)-poly(lactide); D011092:Polyethylene Glycols; D009553:Nimodipine