title: Optimised nanoformulation of bromocriptine for direct nose-to-brain delivery: biodistribution, pharmacokinetic and dopamine estimation by ultra-HPLC/mass spectrometry method.
abstract: OBJECTIVE
  The present work evaluated whether the prepared nanoparticles (NPs) would be able to target the drug to the brain by a non-invasive nasal route enhancing its bioavailability.
  
  
  METHODS
  Bromocriptine (BRC) chitosan NPs (CS NPs) were prepared by ionic gelation method. The biodistribution, pharmacokinetic parameters and dopamine concentration was analysed by ultra-HPLC/mass spectrometry method. The histopathological examination in haloperidol-induced Parkinson's disease in mice model following intranasal (i.n.) administration was evaluated.
  
  
  RESULTS
  BRC was found stable in all exposed conditions and the percentage accuracy observed for intra-day and inter-day batch samples ranged from 90.5 to 107% and 95.3 to 98.9% for plasma and brain homogenates, respectively. BRC-loaded CS NPs showed greater retention into the nostrils (42 ± 8.5% radioactivity) for about 4 h, whereas the 44 ± 7.5% could be retained up to 1 h for BRC solution. The brain:blood ratios of 0.96 ± 0.05 > 0.73 ± 0.15 > 0.25 ± 0.05 of BRC-loaded CS NPs (i.n.) > BRC solution (i.n.) > BRC-loaded CS NPs (intravenous), respectively, at 0.5 h indicated direct nose-to-brain transport bypassing blood-brain barrier. BRC-loaded CS NPs administered intranasally showed significantly high dopamine concentration (20.65 ± 1.08 ng/ml) as compared to haloperidol-treated mice (10.94 ± 2.16 ng/ml) (p < 0.05). Histopathology of brain sections showed selective degeneration of the dopaminergic neurons in haloperidol-treated mice which was markedly reverted by BRC-loaded CS NPs.
  
  
  CONCLUSIONS
  Nanoparticulate drug delivery system could be potentially used as a nose-to-brain drug delivery carrier for the treatment of Parkinson's disease.
authors.affiliation: Department of Pharmaceutics, Jamia Hamdard, Faculty of Pharmacy , Hamdard Nagar, New Delhi-110062 , India +91 9811312247 ; +011 26059633 ; javedaali@ yahoo.com.
authors.forename: Shadab
authors.initials: S
authors.lastname: Md
authors.forename: Shadabul
authors.initials: S
authors.lastname: Haque
authors.forename: Mohammad
authors.initials: M
authors.lastname: Fazil
authors.forename: Manish
authors.initials: M
authors.lastname: Kumar
authors.forename: Sanjula
authors.initials: S
authors.lastname: Baboota
authors.forename: Jasjeet K
authors.initials: JK
authors.lastname: Sahni
authors.forename: Javed
authors.initials: J
authors.lastname: Ali
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000978:Antiparkinson Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D001692:Biological Transport; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D001971:Bromocriptine / Q000737:chemistry / Q000493:pharmacokinetics*; D048271:Chitosan / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004298:Dopamine / Q000032:analysis; D016503:Drug Delivery Systems; D005260:Female; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D009297:Nasal Mucosa / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*; D019275:Radiopharmaceuticals; D013670:Sodium Pertechnetate Tc 99m; D014018:Tissue Distribution
chemical_list: D000978:Antiparkinson Agents; D019275:Radiopharmaceuticals; D001971:Bromocriptine; D048271:Chitosan; D013670:Sodium Pertechnetate Tc 99m; D004298:Dopamine
keywords: Parkinson's disease; bromocriptine; chitosan; dopamine; nanoparticles; nasal retention