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.

Enhancement of systemic and CNS delivery of meptazinol hydrochloride by intranasal administration to rats.

AIM: To investigate the extent of systemic absorption and uptake of meptazinol (MEP) hydrochloride in cerebrospinal fluid (CSF) after intranasal administration on rats and compare with oral administration. METHODS: CSF samples were collected by a serial sampling method. The concentration of MEP in the biological samples was measured by HPLC with fluorescence detector. RESULTS: Rapid and significant levels of MEP in plasma and CSF can be achieved after nasal administration whereas the oral administration resulted in considerably lower drug concentrations. AUC in plasma and CSF from the nasal route are 7.375 and 15.6 folds compared with those of the oral route, respectively. CONCLUSION: Intranasal MEP is able to show quick absorption and improve the bioavailability, which could be a promising alternative to oral administration.

Effects of intranasal administration of nimodipine on cerebral hemodynamics of dogs.

AIM: To investigate the effect of nimodipine (NM) on cerebral blood flow (CBF) in dogs following intranasal administration. METHODS: NM solution was administered intranasally, intravenously (i.v.), and orally to dogs and the change of CBF was determined by using electromagnetic blood flowmeter. MFLab experimental program was applied to monitor the experimental process and analyze data. RESULTS: CBF markedly increased after iv and intranasal application, while large variance was observed after oral dosing. CBF in dogs after three administrations increased by 26.4%, 28.0% and 8.5%, respectively, compared with that of baseline. Following intranasal administration, the onset of action was slightly slower than that after iv injection [(5 +/- 4) min vs (2.2 +/- 1.2) min], however the duration of improvement was the longest [ (25 +/- 17) min]. CONCLUSION: Intranasal delivery for NM can be a promising alternative to parenteral or oral administration.