Nanocrystal formulations of a poorly soluble drug. 2. Evaluation of nanocrystal liver uptake and distribution after intravenous administration to mice

Publication date: 30 May 2017 Source:International Journal of Pharmaceutics, Volume 524, Issues 1–2 Author(s): Kalle Sigfridsson, Pia Skantze, Urban Skantze, Lena Svensson, Lars Löfgren, Pär Nordell, Erik Michaëlsson, Bård Smedsrød, Britt Fuglesteg, Kjetil Elvevold, Lennart Lindfors A stabilized high drug load intravenous formulation could allow compounds with less optimal pharmacokinetic profiles to be developed. Polyethylene glycol (PEG)-ylation is a frequently used strategy for particle delivery systems to avoid the liver, thereby extending blood circulation time. The present work reports the mouse in vivo distribution after i.v. administration of a series of nanocrystals prepared with the bead milling technique and PEG-ylated with DSPE-PEG2000 and Pluronic F127, with and without polyvinylpyrrolidone K30 (PVP)/Aerosol OT (AOT) as primary stabilizers. While all formulations were cleared significantly faster than expected from nanocrystal dissolution alone, purely DSPE-PEG2000 PEG-ylated particles displayed prolonged circulation time (particles elimination half-life of 9min) compared to DSPE-PEG2000/PVP/AOT formulation (half-life of 3min). The two Pluronic F127 stabilized formulations displayed similar half-lives (9min with and without PVP/AOT, respectively). Whole tissue kinetics shows that clearance of particles could be attributed to accumulation in the liver. A separate in vivo study addressed the liver cell distribution after administration. Dissolve...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research