title: Influence of polymeric microcarriers on the in vivo intranasal uptake of an anti-migraine drug for brain targeting.
abstract: The objective of this study was to investigate the effect of polymeric microcarriers on the in vivo intranasal uptake of an anti-migraine drug for brain targeting. Mucoadhesive powder formulations consisted of antimigraine drug, zolmitriptan, and chitosans (various molecular weights and types) or hydroxypropyl methylcellulose (HPMC). Their suitability for nasal administration was evaluated by in vitro and ex vivo mucoadhesion and permeation tests. The formulations based on chitosan glutamate (CG) or HPMC were tested in vivo because they showed good mucoadhesive properties and altered the permeation rate of the drug. The in vivo results from intravenous infusion and nasal aqueous suspension of the drug or nasal particulate powders were compared. The plasmatic AUC values obtained within 8h following intravenous administration appeared about three times higher than those obtained by nasal administration, independent of the formulations. Zolmitriptan concentrations in the cerebrospinal fluid obtained from nasal and intravenous administrations were, respectively, 30 and 90 times lower than the concentrations of the drug in the blood. Thus, nasal administration potentiated the central zolmitriptan activity, allowing a reduction in the drug peripheral levels, with respect to the intravenous administration. Among nasally administered formulations, CG microparticles showed the highest efficacy in promoting the central uptake of zolmitriptan within 1h.
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy. Electronic address: eligav@uniss.it.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gavini
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy. Electronic address: grassu@uniss.it.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Rassu
authors.affiliation: Department of Experimental and Clinical Medicine, University of Ferrara, Ferrara, Italy. Electronic address: frl@unife.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Ferraro
authors.affiliation: Department of Experimental and Clinical Medicine, University of Ferrara, Ferrara, Italy. Electronic address: sarah.beggiato@unife.it.
authors.forename: Sarah
authors.initials: S
authors.lastname: Beggiato
authors.affiliation: Department of Health Sciences, Luleå University of Technology, Luleå, Sweden. Electronic address: amjalh@ltu.se.
authors.forename: Amjad
authors.initials: A
authors.lastname: Alhalaweh
authors.affiliation: Department of Health Sciences, Luleå University of Technology, Luleå, Sweden. Electronic address: sitvel@ltu.se.
authors.forename: Sitaram
authors.initials: S
authors.lastname: Velaga
authors.affiliation: Department of Chemistry, University of Ferrara, Ferrara, Italy. Electronic address: mrcncl@unife.it.
authors.forename: Nicola
authors.initials: N
authors.lastname: Marchetti
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Sassari, Italy. Electronic address: bandiera@uniss.it.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Bandiera
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy. Electronic address: pgiunc@uniss.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Giunchedi
authors.affiliation: Department of Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy. Electronic address: dla@unife.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Dalpiaz
mesh_terms: D000269:Adhesives / Q000008:administration & dosage / Q000737:chemistry; D000281:Administration, Intranasal / Q000379:methods; D061605:Administration, Intravenous / Q000379:methods; D000818:Animals; D019540:Area Under Curve; D001921:Brain / Q000187:drug effects*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D018698:Glutamic Acid / Q000008:administration & dosage / Q000737:chemistry; D065347:Hypromellose Derivatives / Q000008:administration & dosage / Q000737:chemistry; D008881:Migraine Disorders / Q000188:drug therapy*; D009297:Nasal Mucosa / Q000187:drug effects; D023303:Oxazolidinones / Q000008:administration & dosage / Q000737:chemistry; D010539:Permeability; D011108:Polymers / Q000008:administration & dosage*; D011208:Powders / Q000008:administration & dosage / Q000737:chemistry; D013552:Swine; D014363:Tryptamines / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000269:Adhesives; D004337:Drug Carriers; D023303:Oxazolidinones; D011108:Polymers; D011208:Powders; D014363:Tryptamines; C089750:zolmitriptan; D018698:Glutamic Acid; D065347:Hypromellose Derivatives; D048271:Chitosan