title: Haloperidol-loaded intranasally administered lectin functionalized poly(ethylene glycol)-block-poly(D,L)-lactic-co-glycolic acid (PEG-PLGA) nanoparticles for the treatment of schizophrenia.
abstract: Lectin-functionalized, polyethylene glycol-block-poly-(D,L)-lactic-co-glycolic acid nanoparticles loaded with haloperidol were prepared with narrow size distributions and sizes <135nm. The nanoparticles exhibited high Solanum tuberosum lectin (STL) conjugation efficiencies, encapsulation efficiencies, and drug loading capacities. The in vitro release of haloperidol was 6-8% of the loaded amount in endo-lysosomal conditions over 96h, demonstrating minimal drug leakage and the potential for the efficient drug transport to the targeted brain tissue. The haloperidol released upon erosion was successful in displacing [(3)H] N-propylnorapomorphine and binding to bovine striatal dopamine D2 receptors. Both haloperidol-loaded nanoparticle formulations were found to be highly effective at inducing catalepsy. Intranasal administration of STL-functionalized nanoparticles increased the brain tissue haloperidol concentrations by 1.5-3-fold compared to non-STL-functionalized particles and other routes of administration. This formulation demonstrates promise in the reduction of the drug dose necessary to produce a therapeutic effect with antipsychotic drugs for the treatment of schizophrenia.
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Canada.
authors.forename: Justin
authors.initials: J
authors.lastname: Piazza
authors.affiliation: Department of Chemical Engineering, McMaster University, Hamilton, Canada.
authors.forename: Todd
authors.initials: T
authors.lastname: Hoare
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Canada.
authors.forename: Luke
authors.initials: L
authors.lastname: Molinaro
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Canada.
authors.forename: Kristen
authors.initials: K
authors.lastname: Terpstra
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Canada.
authors.forename: Jayant
authors.initials: J
authors.lastname: Bhandari
authors.affiliation: Department of Mechanical Engineering, McMaster University, Hamilton, Canada.
authors.forename: P Ravi
authors.initials: PR
authors.lastname: Selvaganapathy
authors.affiliation: Department of Biology, McMaster University, Hamilton, Canada.
authors.forename: Bhagwati
authors.initials: B
authors.lastname: Gupta
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Canada. Electronic address: mishrar@mcmaster.ca.
authors.forename: Ram K
authors.initials: RK
authors.lastname: Mishra
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D002375:Catalepsy / Q000139:chemically induced / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D065546:Drug Liberation; D006220:Haloperidol / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D037102:Lectins / Q000737:chemistry*; D008297:Male; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism; D013499:Surface Properties
chemical_list: D004337:Drug Carriers; D037102:Lectins; D011091:Polyesters; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D011092:Polyethylene Glycols; D006220:Haloperidol
keywords: Blood–brain barrier; Cell targeting; Haloperidol; Intranasal administration; PEG–PLGA nanoparticles; Schizophrenia; Solanum tuberosum lectin