Distribution of an intravenous injectable nimodipine nanosuspension in mice.
The distribution of an intravenous injectable nimodipine nanosuspension with mean particle size of both 300 and 650 nm in mice was systemically investigated compared with that of a nimodipine ethanol formulation (Nimotop) and a nanosuspension coated with Tween-80. The results showed that the 650-nm nanoparticles provided significantly higher drug concentrations in the liver, spleen and lungs because of their capture by Kupffer cells in the mononuclear phagocyte system, but lower drug concentrations in the brain compared with Nimotop and smaller nanoparticles. These nanoparticles failed to give increased brain concentrations even when coated with Tween-80. The 300-nm nanoparticles could effectively increase drug concentrations in the brain and remarkably reduce drug concentrations in the liver, spleen and lungs, indicating that the nimodipine nanosuspension may be a promising formulation with no ethanol, but the particle size must be small.
Xiong
Ruolan
R
Division of Pharmaceutics, Shanghai Institute of Pharmaceutical Industry, ZhongShanBeiYi Road 1111, Shanghai 200437, China.
Lu
Weigen
W
Yue
Peng
P
Xu
Rong
R
Li
Jun
J
Chen
Tingting
T
Wang
Peiquan
P
D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000431:Ethanol / Q000737:chemistry; D005079:Excipients / Q000737:chemistry*; D007275:Injections, Intravenous; D007728:Kupffer Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D053758:Nanoparticles; D009553:Nimodipine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013535:Suspensions; D014018:Tissue Distribution
D002121:Calcium Channel Blockers; D005079:Excipients; D011136:Polysorbates; D012997:Solvents; D013535:Suspensions; D000431:Ethanol; D009553:Nimodipine