title: Multifunctional liposomes for nasal delivery of the anti-Alzheimer drug tacrine hydrochloride.
abstract: The purpose of this study was the development of multifunctional liposomes for nasal administration of tacrine hydrochloride. Liposomes were prepared using traditional excipients (cholesterol and phosphatidylcholine), partly enriched with α-tocopherol and/or Omega3 fatty acids. This approach was chosen in order to obtain at the same time two positive results: an enhanced drug permeation through nasal mucosa and a concomitant neuroprotective effect. Several liposome formulations were prepared using the Reverse Phase Evaporation technique followed by membrane filter extrusion. In particular, liposome capacity to enhance drug permeation was evaluated by means of membrane permeation and cellular uptake studies. Furthermore, liposome effect on neuronal viability and intracellular ROS production was evaluated as well as their cytoprotective effect against oxidative stress. All liposome formulations showed a mean diameter in the range of 175 nm to 219 nm with polydispersity index lower than 0.22, a lightly negative zeta potential and excellent encapsulation efficiency. Moreover, along with good mucoadhesive properties, multifunctional liposomes showed a markedly increase in tacrine permeability, which can be related to liposome fusion with cellular membrane, a hypothesis, which was also supported by cellular uptake studies. Finally, the addition of α-tocopherol without Omega3 fatty acids, was found to increase the neuroprotective activity and antioxidant properties of liposomes.
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna , Via San Donato, Bologna , Italy .
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Corace
authors.forename: Cristina
authors.initials: C
authors.lastname: Angeloni
authors.forename: Marco
authors.initials: M
authors.lastname: Malaguti
authors.forename: Silvana
authors.initials: S
authors.lastname: Hrelia
authors.forename: Paul C
authors.initials: PC
authors.lastname: Stein
authors.forename: Martin
authors.initials: M
authors.lastname: Brandl
authors.forename: Roberto
authors.initials: R
authors.lastname: Gotti
authors.forename: Barbara
authors.initials: B
authors.lastname: Luppi
mesh_terms: D000268:Adhesiveness; D000281:Administration, Intranasal; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004339:Drug Compounding; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes; D008561:Membrane Fusion / Q000187:drug effects; D009297:Nasal Mucosa / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018697:Nootropic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D034561:Sheep, Domestic; D013619:Tacrine / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D004337:Drug Carriers; D008081:Liposomes; D018697:Nootropic Agents; D013619:Tacrine
keywords: Antioxidant activity; enhanced permeation; nasal administration; neuronal uptake