title: Ligustrazine phosphate ethosomes for treatment of Alzheimer's disease, in vitro and in animal model studies.
abstract: In the present study, we have investigated transdermal administration of ligustrazine phosphate (LP), as an antioxidant, for the treatment of Alzheimer's disease (AD). The LP transdermal ethosomal system was designed and characterized. Franz-type diffusion cells and confocal laser scanning microscopy were used for the in vitro permeation studies. Furthermore, the effect of LP transdermal ethosomal system on AD was evaluated in the scopolamine-induced amnesia rats by evaluating the behavioral performance in the Morris water maze test. The activities of the antioxidant enzymes and the levels of the lipid peroxidation product malondialdehyde (MDA) in the brain of rats were also determined. The results showed that both the penetration ability and the drug deposition in skin of the LP ethosomal system were significantly higher than the aqueous one. The LP transdermal ethosomal system could recover the activities of the antioxidant enzymes and the levels of MDA in the brain of the amnesic rats to the similar status of the normal rats, which was also indirectly reflected by the improvement in the behavioral performance. In conclusion, LP might offer a potential alternative therapeutic drug in the fight against AD, and ethosomes could be vesicles of choice for transdermal delivery of LP.
authors.affiliation: School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Shi
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wang
authors.forename: Guoan
authors.initials: G
authors.lastname: Luo
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000279:Administration, Cutaneous; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D004337:Drug Carriers; D004924:Escape Reaction / Q000187:drug effects; D000431:Ethanol / Q000737:chemistry; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008568:Memory / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D018613:Microscopy, Confocal; D010539:Permeability; D010713:Phosphatidylcholines / Q000737:chemistry; D011719:Pyrazines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012601:Scopolamine; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013482:Superoxide Dismutase / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors
chemical_list: D000180:Acrylic Resins; D000975:Antioxidants; D004337:Drug Carriers; D010713:Phosphatidylcholines; D011719:Pyrazines; C479038:carbomer; D000431:Ethanol; D008315:Malondialdehyde; D012601:Scopolamine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C017953:tetramethylpyrazine