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 μg/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 μM 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.

Chiesa, E., Monti, L., Paganini, C., Dorati, R., Conti, B., Modena, T., et al. (2017). Polyethylene Glycol-Poly-Lactide-co-Glycolide Block Copolymer-Based Nanoparticles as a Potential Tool for Off-Label Use of N-Acetylcysteine in the Treatment of Diastrophic Dysplasia. JOURNAL OF PHARMACEUTICAL SCIENCES, 106(12), 3631-3641 [10.1016/j.xphs.2017.08.004].

Polyethylene Glycol-Poly-Lactide-co-Glycolide Block Copolymer-Based Nanoparticles as a Potential Tool for Off-Label Use of N-Acetylcysteine in the Treatment of Diastrophic Dysplasia.

Monti L;Conti B;Rossi A;
2017-01-01

Abstract

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 μg/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 μM 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.
2017
Chiesa, E., Monti, L., Paganini, C., Dorati, R., Conti, B., Modena, T., et al. (2017). Polyethylene Glycol-Poly-Lactide-co-Glycolide Block Copolymer-Based Nanoparticles as a Potential Tool for Off-Label Use of N-Acetylcysteine in the Treatment of Diastrophic Dysplasia. JOURNAL OF PHARMACEUTICAL SCIENCES, 106(12), 3631-3641 [10.1016/j.xphs.2017.08.004].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/1052578
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