title: Brain Targeting of a Water Insoluble Antipsychotic Drug Haloperidol via the Intranasal Route Using PAMAM Dendrimer.
abstract: Delivery of therapeutics to the brain is challenging because many organic molecules have inadequate aqueous solubility and limited bioavailability. We investigated the efficiency of a dendrimer-based formulation of a poorly aqueous soluble drug, haloperidol, in targeting the brain via intranasal and intraperitoneal administration. Aqueous solubility of haloperidol was increased by more than 100-fold in the developed formulation. Formulation was assessed via different routes of administration for behavioral (cataleptic and locomotor) responses, and for haloperidol distribution in plasma and brain tissues. Dendrimer-based formulation showed significantly higher distribution of haloperidol in the brain and plasma compared to a control formulation of haloperidol administered via intraperitoneal injection. Additionally, 6.7 times lower doses of the dendrimer-haloperidol formulation administered via the intranasal route produced behavioral responses that were comparable to those induced by haloperidol formulations administered via intraperitoneal injection. This study demonstrates the potential of dendrimer in improving the delivery of water insoluble drugs to brain.
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University , Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Yogesh K
authors.initials: YK
authors.lastname: Katare
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University , Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Ritesh P
authors.initials: RP
authors.lastname: Daya
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University , Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Christal
authors.initials: C
authors.lastname: Sookram Gray
authors.affiliation: Department of Chemistry, McMaster University , Hamilton, Ontario L8S 4M1, Canada.
authors.forename: Roger E
authors.initials: RE
authors.lastname: Luckham
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University , Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Jayant
authors.initials: J
authors.lastname: Bhandari
authors.affiliation: School of Pharmacy, Concordia University Wisconsin , Mequon, Wisconsin 53097, United States.
authors.forename: Abhay S
authors.initials: AS
authors.lastname: Chauhan
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University , Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Ram K
authors.initials: RK
authors.lastname: Mishra
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001682:Biological Availability; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006220:Haloperidol / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D014150:Antipsychotic Agents; D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; D006220:Haloperidol
keywords: brain targeting; dendrimers; drug delivery; haloperidol; intranasal administration; nanotechnology