Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 106, Issue 12, Pages 3631-3641Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.xphs.2017.08.004
Keywords
nanoparticles; PLGA; polymeric drug delivery systems; biodegradable polymers; freeze-drying/lyophilization; nanotechnology
Funding
- European Community [602300]
- PRIN [2015F3JHMB]
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Potential off-label therapeutic role of N-acetylcysteine (N-Ac) was recently demonstrated in the treatment of diastrophic dysplasia (DTD) using mutant mice; its main drawback is the rapid clearance from blood due to the liver metabolism. Our goal was to investigate the potential of polyethylene glycol polylactide-co-glycolide block copolymer (PLGA-PEG)-based nanoparticles (NPs) in order to improve in vivo biodistribution performances and N-Ac pharmacokinetic profile after subcutaneous administration in mice. Results suggest that N-Ac can be effectively loaded into NPs (about 99 mu g/mg NPs) using a suitably optimized nanoprecipitation method. Thanks to the good physical characteristics (mean diameter <100 nm, zeta potential about -8 mV) NPs can reach skeletal tissue in particular femoral head and proximal tibia epiphysis at the sixth hour after injection, remaining in the tissues till 24 h. Furthermore, pharmacokinetic study revealed a sustained N-Ac concentration in plasma with a peak concentration of 2.48 +/- 1.72 mu M at the 24th hour after injection. Overall, results highlight the actual interest of N-Ac-loaded PLGA-PEG NPs as useful platform for N-Ac parenteral administration. (C) 2017 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
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