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Title: N-acetylcysteine-loaded PLGA nanoparticles outperform conventional N-acetylcysteine in acute lung injuries in vivo
Journal: International Journal of Polymeric Materials and Polymeric Biomaterials
Author: 1. Ali Akbar Karimi Zarchi, 1,5. Amir Amani, 2. Mohammad Ali Faramarzi, 3. Kambiz Gilani, 4. Mahmood Ghazi-Khansari, Guiti Ghamami
Year: 2017
Address: 1. Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran 2. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran, 3. Aerosol Research Laboratory, Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences 4. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 5. Medical Biomaterials Research Center, Tehran University of Medical Sciences, Tehran, Iran
Abstract: Antioxidants potentially play an important role in the control and treatment of acute lung injury (ALI). In this study, for the first time, antioxidant effect of Nacetylcysteine (NAC) was evaluated in-vivo when loaded in a polymeric nanoparticle. NACloaded PLGA nanoparticles (NACPLGA NPs) were prepared by electrospray method (electrohydrodynamic atomization) and assessed in animals with direct exposure to lipopolysaccharide (LPS). Size, polydispersity index and zeta potential of NAC-PLGA NPs were 197.5 nm, 0.21 and -10.4, respectively. Fine particle fraction (FPF) and emitted dose were 13.71% and 47.75%, respectively. Compared to the control group, pretreatment of LPS challenged rats with NACPLGA NPs led to a significant increase in concentration of NAC in bronchoalveolar lavage fluid (BALF) and pulmonary non‐ protein thiols levels as well as decrease in lung wet/dry weight ratio, protein concentrations, inflammatory cell counts and levels of pulmonary myeloperoxidase and malondialdehyde. Additionally, the group showed that pulmonary architecture was preserved and infiltration of inflammatory cells and edema decreased, with lesser degree of alveolar congestion and haemorrhage. Pretreatment of animals with conventional NAC or empty PLGA NPs did not show a significant change in the above mentioned injury indicators. In conclusion, NAC, when delivered in a polymeric nanoparticle formulation, shows improved efficacy in preventing LPSinduced lung injury by reducing the effects of ROS and inflammation. Effectiveness of NACPLGA NPs can be attributed to the ability of nanoparticles to deliver NAC directly to the lung with increased retention and higher pulmonary concentrations of NAC in the lung.
Keywords: Acute lung injury, PLGA, Nacetylcysteine, electrospray, lipopolysaccharide
Application: Drug Delivery
Product Model 1: Syringe Pump (SP1000HOM)
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URL: http://www.tandfonline.com/doi/abs/10.1080/00914037.2016.1236339#="http://www.tandfonline.com" & "/doi/abs/10.1080/00914037.2016.1236339"#