title: Preparation, macrophages targeting delivery and anti-inflammatory study of pentapeptide grafted nanostructured lipid carriers.
abstract: The targeting ability of pentapeptide (Thr-Lys-Pro-Pro-Arg) grafted nanostructured lipid carriers (Pen-NLCs) to macrophages was investigated in both in vitro and in vivo studies. The results showed the improvement of the anti-inflammatory effect by using this drug delivery system. Firstly, a pentapeptide-polyethylene glycol2000-stearate was synthesized and formulated into Pen-NLCs. Non-grafted nanostructured lipid carriers (Bare-NLCs) and Pen-NLCs were 190.0±1.0 and 203.0±8.5 nm in size, -8.1±2.1 and 2.3±1.2 mV in zeta potential respectively. Meanwhile, they had comparable entrapment efficiency and drug loading efficiency. In vitro and in vivo cellular uptake studies showed increased internalization of Pen-NLCs by macrophages when compared to pure drugs and Bare-NLCs. Animal studies in a carrageenan-treated air pouch model were used to further investigate the anti-inflammatory effects of Pen-NLCs. Through intravenous administration, a single dose of DXM loaded Pen-NLCs showed the strongest inhibition of inflammatory indexes of air pouch fluid weight, leukocyte infiltration, granulation tissue weight and nitric oxide concentration in comparison with free drugs and DXM loaded Bare-NLCs. In conclusion, this study demonstrated the potential of Pen-NLCs as promising drug carriers for anti-inflammatory treatments.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery, Ministry of Education, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, PR China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhao
authors.forename: Tingting
authors.initials: T
authors.lastname: Fan
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Meilin
authors.initials: M
authors.lastname: Wu
authors.forename: Lian
authors.initials: L
authors.lastname: Li
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Jian
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry; D002351:Carrageenan; D002460:Cell Line; D003907:Dexamethasone / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D007958:Leukocyte Count; D008264:Macrophages; D008297:Male; D051379:Mice; D049329:Nanostructures / Q000737:chemistry; D009569:Nitric Oxide / Q000276:immunology; D009842:Oligopeptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013228:Stearates / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D009842:Oligopeptides; D013228:Stearates; D009569:Nitric Oxide; D011092:Polyethylene Glycols; D003907:Dexamethasone; D002351:Carrageenan