title: Neuroprotective Effects of Human Serum Albumin Nanoparticles Loaded With Brimonidine on Retinal Ganglion Cells in Optic Nerve Crush Model.
abstract: OBJECTIVE
  We investigated the neuroprotective effect of human serum albumin nanoparticles (HSA-NPs) and their conjugation with brimonidine (HSA-Br-NPs) on retinal ganglion cells (RGCs) in optic nerve crush (ONC) model.
  
  
  METHODS
  We fabricated HSA-Br-NPs by ethanol precipitation, including 0.18% brimonidine (Br) and 3.5% human serum albumin (HSA) in HSA-Br-NP solution. We performed ONC and intravitreal injection in Sprague-Dawley rats, which were divided into (1) Normal, (2) balanced salt solution (BSS)-injected ONC, (3) HSA-NP-injected ONC, (4) Br-injected ONC, and (5) HSA-Br-NP-injected ONC groups. Survival of RGC was compared 5 and 14 days after procedures. A cell viability assay evaluated the amyloid-β (Aβ)-associated neuroprotective mechanism of HSA-NP.
  
  
  RESULTS
  The HSA-Br-NPs showed a narrow size distribution (152.8 ± 51.1 nm) and a negatively charged surface (-29.7 ± 7.5 mV), releasing Br for 5 days. The percentages of RGC survival in the HSA-NP (52.6 ± 3.3%), Br (58.0 ± 4.2%), and HSA-Br-NP (63.5 ± 7.1%) groups relative to Normal (100%) were significantly higher than in the BSS group (29.2 ± 3.3%) 5 days after ONC (P < 0.001). However, the HSA-Br-NP (38.1 ± 3.6%) group showed significantly higher RGC density than the BSS (10.3 ± 5.6%, P < 0.001) or Br (18.6 ± 3.9%, P = 0.006) group at 14 days. The HSA-NP injection reduced Aβ deposition in the RGC layer of ONC model, and a cell viability test showed that HSA-NP can inhibit Aβ-induced RGC death.
  
  
  CONCLUSIONS
  Human serum albumin nanoparticles showed neuroprotective potential by inhibiting Aβ deposition, and exerted a sustained therapeutic effect with the combined neuroprotective agent. Our results suggest the potential of HSA-Br-NP as a promising neuroprotective agent.
authors: Department of Ophthalmology Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors: Ko Eun
authors: KE
authors: Kim
authors: Department of Chemical & Biomolecular Engineering, Sogang University, Mapo-Gu, Seoul, South Korea.
authors: Inseok
authors: I
authors: Jang
authors: Department of Chemical & Biomolecular Engineering, Sogang University, Mapo-Gu, Seoul, South Korea.
authors: Hyungwon
authors: H
authors: Moon
authors: Department of Ophthalmology Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors: Yu Jeong
authors: YJ
authors: Kim
authors: Department of Ophthalmology Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors: Jin Wook
authors: JW
authors: Jeoung
authors: Department of Ophthalmology Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors: Ki Ho
authors: KH
authors: Park
authors: Department of Chemical & Biomolecular Engineering, Sogang University, Mapo-Gu, Seoul, South Korea.
authors: Hyuncheol
authors: H
authors: Kim
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage; D000818:Animals; D000068438:Brimonidine Tartrate; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004337:Drug Carriers; D006801:Humans; D007150:Immunohistochemistry; D058449:Intravitreal Injections; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage*; D009409:Nerve Crush / Q000379:methods*; D009900:Optic Nerve / Q000187:drug effects / Q000473:pathology*; D020221:Optic Nerve Injuries / Q000188:drug therapy* / Q000473:pathology; D011810:Quinoxalines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D012709:Serum Albumin
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D004337:Drug Carriers; D011810:Quinoxalines; D012709:Serum Albumin; D000068438:Brimonidine Tartrate