title: Targeting brain cells with glutathione-modulated nanoliposomes: in vitro and in vivo study.
abstract: BACKGROUND
  The blood-brain barrier prevents many drug moieties from reaching the central nervous system. Therefore, glutathione-modulated nanoliposomes have been engineered to enhance the targeting of flucytosine to the brain.
  
  
  METHODS
  Glutathione-modulated nanoliposomes were prepared by thin-film hydration technique and evaluated in the primary brain cells of rats. Lecithin, cholesterol, and span 65 were mixed at 1:1:1 molar ratio. The molar percentage of PEGylated glutathione varied from 0 mol% to 0.75 mol%. The cellular binding and the uptake of the targeted liposomes were both monitored by epifluorescent microscope and flow cytometry techniques. A biodistribution and a pharmacokinetic study of flucytosine and flucytosine-loaded glutathione-modulated liposomes was carried out to evaluate the in vivo brain-targeting efficiency.
  
  
  RESULTS
  The size of glutathione-modulated nanoliposomes was <100 nm and the zeta potential was more than -65 mV. The cumulative release reached 70% for certain formulations. The cellular uptake increased as molar percent of glutathione increased to reach the maximum at 0.75 mol%. The uptake of the targeted liposomes by brain cells of the rats was three times greater than that of the nontargeted liposomes. An in vivo study showed that the relative efficiency was 2.632±0.089 and the concentration efficiency was 1.590±0.049, and also, the drug-targeting index was 3.670±0.824.
  
  
  CONCLUSIONS
  Overall, these results revealed that glutathione-PEGylated nanoliposomes enhance the effective delivery of flucytosine to brain and could become a promising new therapeutic option for the treatment of the brain infections.
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Beni-suef University, Assuit, Egypt.
authors.forename: Heba F
authors.initials: HF
authors.lastname: Salem
authors.affiliation: Department of Industrial Pharmacy, Assiut University, Egypt.
authors.forename: Sayed M
authors.initials: SM
authors.lastname: Ahmed
authors.affiliation: Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assuit, Egypt.
authors.forename: Ashraf E
authors.initials: AE
authors.lastname: Hassaballah
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Beni-suef University, Assuit, Egypt ; Department of Pharmaceutics and Industrial Pharmacy, Deraya University, Egypt.
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: Omar
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry; D005434:Flow Cytometry; D005437:Flucytosine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005978:Glutathione / Q000737:chemistry*; D008081:Liposomes; D008297:Male; D053758:Nanoparticles; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D000935:Antifungal Agents; D005079:Excipients; D008081:Liposomes; D011092:Polyethylene Glycols; D005437:Flucytosine; D005978:Glutathione
keywords: brain-targeting; glutathione-modulated nanoliposomes; nanoliposomes