title: Anti-inflammatory activity of injectable dexamethasone acetate-loaded nanostructured lipid carriers.
abstract: This work studied the intravenous injection formulation of nanostructured lipid carriers (NLCs) loaded with dexamethasone acetate (DA), a poorly water-soluble drug. The goal of this study was to design nanoparticles which could improve therapeutic efficacy of DA on inflammations. Based on the optimized results of single-factor screening experiment, DA-loaded NLCs (DA-NLCs) prepared by an emulsification-ultrasound method were found to be relatively uniform in size (178 ± 4 nm) with a negative zeta potential (-38 ± 4 mV). The average drug entrapment efficiency was 91 ± 3 %. In vitro release tests indicated DA-NLCs possessed a sustained release characteristic and the accumulative release percentage was near 80 % at 23 h. DA-NLCs exhibited an average peak concentration of DA (7.6 μg/ml) in the pleural exudate after intravenous administration to an experimental model of γ-carrageenan-induced pleuritis rats, which was 8.3 times higher than that of free DA (0.9 μg/ml). The γ-carrageenan-induced edema test showed that the anti-acute inflammatory activity of DA-NLCs was stronger than that of free drug at the same drug concentration (P<0.05). In addition, biodistribution results clearly indicated that DA-NLCs preferentially accumulated in mice livers and lungs after intravenous injection. These results revealed that injectable NLCs may serve as a promising carrier for DA, greatly enhancing the selective effect on inflammatory sites, reducing systematic side effects and may be a potential carrier to increase therapeutic efficacy on inflammatory diseases.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, P.R. China.
authors.forename: Xuefan
authors.initials: X
authors.lastname: Xu
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhao
authors.forename: Hongyun
authors.initials: H
authors.lastname: Yang
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Jian
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D007275:Injections, Intravenous; D008055:Lipids / Q000737:chemistry; D008297:Male; D051379:Mice; D053758:Nanoparticles; D010316:Particle Size; D010998:Pleurisy / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D012995:Solubility; D014018:Tissue Distribution
chemical_list: D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008055:Lipids; D003907:Dexamethasone; C018038:dexamethasone acetate