ABSTRACT
The purpose of the present study was to investigate the possibility of targeting an anti-Alzheimer's drug tacrine in the brain using polymeric nanoparticles. Rats obtained 1mg/kg of tacrine by intravenous injection in the form of three preparations: (1) a simple solution in phosphate buffered saline, (2) bound to poly(n-butylcyanoacrylate) nanoparticles, and (3) bound to poly(n-butylcyanoacrylate) nanoparticles coated with 1% polysorbate 80 (Tween 80). After 1h of post injection the rats were killed by decapitation and tacrine concentration in brain, liver, lungs, spleen and kidneys was analyzed by HPLC. A higher concentration of drug tacrine was observed in liver, spleen and lungs with the nanoparticles in comparison to the free drug. The accumulation of drug tacrine in the liver and spleen was reduced, when nanoparticles were coated with 1% polysorbate 80. In the brain a significant increase in tacrine concentration was observed in the case of poly(n-butylcyanoacrylate) nanoparticles coated with 1% polysorbate 80 compared to the uncoated nanoparticles and the free drug. In conclusion, the present study demonstrates that the brain concentration of intravenously injected tacrine can be enhanced by binding to poly(n-butylcyanoacrylate) nanoparticles, coated with 1% the nonionic surfactant polysorbate 80.
Subject(s)
Brain/metabolism , Cholinesterase Inhibitors/metabolism , Drug Carriers , Enbucrilate/chemistry , Nanoparticles , Polysorbates/chemistry , Surface-Active Agents/chemistry , Tacrine/metabolism , Animals , Blood-Brain Barrier/metabolism , Chemistry, Pharmaceutical , Cholinesterase Inhibitors/administration & dosage , Cholinesterase Inhibitors/chemistry , Drug Stability , Injections, Intravenous , Kinetics , Particle Size , Rats , Rats, Wistar , Solubility , Tacrine/administration & dosage , Tacrine/chemistry , Technology, Pharmaceutical/methodsABSTRACT
Alzheimer's disease is a progressive and fatal neurodegenerative disorder manifested by cognitive and memory deterioration, progressive impairment of activities of daily living, and a variety of neuropsychiatric symptoms and behavioral disturbances. Alzheimer's disease affects 15 million people worldwide and it has been estimated that Alzheimer's disease affects 4.5 million Americans. Rivastigmine is a reversible cholinesterase inhibitor used for the treatment of Alzheimer's disease. Central nervous system drug efficacy depends upon the ability of a drug to cross the blood-brain barrier and reach therapeutic concentrations in brain following systemic administration. The clinical failures of most of the potentially effective therapeutics to treat the central nervous system disorders are often not due to a lack of drug potency but rather shortcomings in the method by which the drug is delivered. Hence, considering the importance of treating Alzheimer's disease, we made an attempt to target the anti-Alzheimer's drug rivastigmine in the brain by using poly(n-butylcyanoacrylate) nanoparticles. The drug was administered as a free drug, bound to nanoparticles and also bound to nanoparticles coated with polysorbate 80. In the brain a significant increase in rivastigmine uptake was observed in the case of poly(n-butylcyanoacrylate) nanoparticles coated with 1% polysorbate 80 compared to the free drug. In conclusion that the present study demonstrates that the brain concentration of intravenously injected rivastigmine can be enhanced over 3.82 fold by binding to poly(n-butylcyanoacrylate) nanoparticles coated with 1% nonionic surfactant polysorbate 80.
