title: Evaluation of brain targeting and mucosal integrity of nasally administrated nanostructured carriers of a CNS active drug, clonazepam.
abstract: OBJECTIVE
  The aim of the study was to target clonazepam, a CNS active drug, to the brain through the non-invasive intranasal (in) route using of nanocarriers with proven safety
  
  
  METHODS
  in clonazepam nanocarriers were prepared by mixing isopropyl myristate, Tween 80, Cremophor EL or lecithin, polyethylene glycol 200, propylene glycol or ethanol in different ratios with water. in-vitro characterization of the nanocarriers was done by various methods including: polarized light microscopy, particle size determination, viscosity measurements and drug release studies. in-vivo study comparing intranasal and intravenous administration was performed. The drug targeting efficiency (DTE %) and direct nose to brain transport percentage (DTP %) were calculated and nasal integrity assessment was carried out.
  
  
  RESULTS
  The obtained formulae had particle size below 100 nm favoring rapid direct nose to brain transport and the time for 100% drug release (T100%) depended on systems composition. Plasma Tmax of clonazepam nanostructured carriers varied from 10-30 min., while their brain Tmax did not exceed 10 min, in comparison with 30 min for iv solution. Although there was no significant difference (p>0.05) between the plasma AUC0-∞ of the different tested nanocarriers and intravenous one, the increase in brain AUC 0 -∞ of different nasal formulations in comparison to that of iv administration (3.6 -7.2 fold) confirms direct nose to brain transport via olfactory region. Furthermore, DTE and DTP% confirmed brain targeting of clonazepam following intranasal administration.
  
  
  CONCLUSIONS
  The results confirmed that intranasal nanocarriers were proved to be safe alternative for iv clonazepam delivery with rapid nose to brain transport.
authors.affiliation: Department of Pharmaceutics, National Organization of Drug Control and Research, Giza, Egypt.
authors.forename: Hend Mohamed
authors.initials: HM
authors.lastname: Abdel-Bar
authors.forename: Amal Youssef
authors.initials: AY
authors.lastname: Abdel-Reheem
authors.forename: Gehanne Abdel Samie
authors.initials: GA
authors.lastname: Awad
authors.forename: Nahed Daoud
authors.initials: ND
authors.lastname: Mortada
mesh_terms: D000281:Administration, Intranasal / Q000379:methods; D000818:Animals; D019540:Area Under Curve; D001692:Biological Transport; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002998:Clonazepam / Q000008:administration & dosage* / Q000378:metabolism*; D004337:Drug Carriers / Q000008:administration & dosage* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D008297:Male; D009092:Mucous Membrane / Q000378:metabolism; D049329:Nanostructures / Q000008:administration & dosage*; D009297:Nasal Mucosa / Q000378:metabolism*; D010316:Particle Size; D051381:Rats; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D002998:Clonazepam