TACRINE HCl NASAL DELIVERY TO CENTRAL NERVOUS SYSTEM USING ANTIOXIDANT LIPOSOMES

Oxidative stress plays an important role in the pathogenesis of the Alzheimer disease, many epidemiological studies have shown an improvement in cognitive activity and a slowing of disease progression following the administration of antioxidant molecules. Furthermore a previous work has shown that α-tocopherol enriched human lipoproteins enhance the survival of developing rat neurons in vitro [1]. It has recently been shown that when the brain is rich in DHA (an omega-3 fatty acid that can also be biosynthesized starting from α-linolenic acid), production of amyloid plaques is lower, with a decrease of characteristic symptoms of the disease [2]. The purpose of this work was the formulation of liposomes for nasal administration of tacrine-HCl. This route has many advantages; in particular is possible to convey the drug directly to the Central Nervous System (CNS), through the olfactory bulb[3] [4] [5]. Part of Tacrine administered can also be absorbed into the systemic circulation avoiding hepatic first pass effect. Liposomes were formulated with ingredients that have a beneficial effect against the disease. In particular, the classical excipients cholesterol (Cho) and phosphatidylcholine (Phc) were enriched with α-tocopherol (Toc) and polyunsaturated fatty acid EPA and DHA (Ω3). This formulative approach allowed us to obtain 100% active liposomes against symptoms of Alzheimer's disease.