title: Phospholipid based colloidal poloxamer-nanocubic vesicles for brain targeting via the nasal route.
abstract: In this study, new phospholipid based colloidal nanocubic vesicles encapsulating olanzapine for its brain targeting via the nasal route were developed. The nanocubic vesicles were prepared by incorporating non-ionic copolymers, poloxamer 188 or 407, in the lipid bilayer. The effect of phospholipid:poloxamer molar ratio on the physicochemical properties of the nanocubic vesicles was investigated. The in vivo behavior and brain targeting of these vesicles were evaluated in rats. TEM photographs showed that the vesicles looked spherical before adding poloxamer. However, after poloxamer incorporation, the vesicles showed a predominant cubic shape, except those containing phospholipid:poloxamer in the molar ratio 5:1 which were spherical. DSC study confirmed perturbation of the packing characteristics as well as fluidization of the lipid bilayer by the polymer with consequent formation of the nanocubic structure. The mean diameter of the vesicles was in the range of 363-645 nm. All vesicles were elastic and the elasticity was found to depend on both poloxamer type and concentration. The intranasal nanocubic vesicles were significantly more efficient in targeting olanzapine to the brain compared to the liposomal vesicles with drug targeting efficiency values of 100% and 80%, respectively, and absolute bioavailability of 37.9% and 14.9%, respectively.
authors: Department of Pharmaceutical Technology, National Research Center, Dokki, Cairo, Egypt.
authors: Hamed A
authors: HA
authors: Salama
authors: Azza A
authors: AA
authors: Mahmoud
authors: Amany O
authors: AO
authors: Kamel
authors: Mayssa
authors: M
authors: Abdel Hady
authors: Gehanne A S
authors: GA
authors: Awad
mesh_terms: D000281:Administration, Intranasal; D061605:Administration, Intravenous; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D001923:Brain Chemistry; D002853:Chromatography, Liquid; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D004548:Elasticity; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D008297:Male; D013058:Mass Spectrometry; D000077152:Olanzapine; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry; D020442:Poloxamer / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D014150:Antipsychotic Agents; D004337:Drug Carriers; D008051:Lipid Bilayers; D008081:Liposomes; D010743:Phospholipids; D020442:Poloxamer; D001569:Benzodiazepines; D000077152:Olanzapine