The central nervous system, one of the most delicate microenvironments of the body, is protected by the blood-brain barrier regulating its homeostasis. Blood-brain barrier is a highly complex structure that tightly regulates the movement of ions of a limited number of small molecules and of an even more restricted number of macromolecules from the blood to the brain, protecting it from injuries and diseases. However, the blood-brain barrier also significantly precludes the delivery of drugs to the brain, thus, preventing the therapy of a number of neurological disorders. As a consequence, several strategies are currently being sought after to enhance the delivery of drugs across the blood-brain barrier. Within this review a brief description of the structural and physiological features of the barriers and the recently born strategy of brain drug delivery based on the use of nanoparticles are described. Finally, the future technological approaches are described. The strong efforts to allow the translation from preclinical to concrete clinical applications are worth the economic investments.
Amyloid β₂₅₋₃₅ (Aβ) peptide may be neurotoxic during the progression of Alzheimer's disease by eliciting reactive oxygen species. The use of folklore medicine is prevalent and plants which possess a rejuvenating property are a large source of natural antioxidants that might afford leads for the development of novel drugs in neurodegenerative disorders. The study was designed to investigate the effect of an ethanol extract of Alpinia galanga (L.) Willd (EAG) on oxidative stress induced Alzheimer's type amnesia in mice. Mice were treated with an experimental extract at 200 mg/kg and 400 mg/kg dose for 14 days and injected with neurotoxic Aβ and the doses were continued for 21 days. Behavioural studies with open field, step-down inhibitory avoidance and a water maze after treatment indicated the acceleration in cognitive function. The elevated levels of acetylcholinesterase and monoamine oxidase enzymes in amnesia induced mice were attenuated by treatment with EAG. The generation of free radicals was decreased due increased activity of antioxidant enzymes after treatment with EAG. These findings suggested that EAG exerts an antiamnesiac effect in Aβ induced neurodegeneration through an antioxidant property.
Alzheimer's disease (AD) is a neurological disorder and is the most frequent type of dementia among elderly people. Donepezil, rivastigmine, galantamine, tacrine and memantine are the US Food and Drug Administration approved oral drugs used in the treatment of AD. Quantitation of these drugs in various biological matrices and monitoring them in long-term treatment is essential to titer the dose of these drugs and ensure patient compliance. This review provides a comprehensive account of various HPLC and LC-MS/MS assays, which have been successfully employed to measure the drug levels in various biological matrices arising from preclinical and clinical studies. In addition, this review collates various considerations such as internal standard selection, extraction schemes, matrix effect, selectivity evaluation and optimization of mass spectrometric conditions to enable the development of sound bioanalytical methods for quantitation of Alzheimer's drugs. Overall LC-MS/MS methods have proven to be the choice of bioanalytical method for the quantification of Alzheimer's drugs in both preclinical and clinical studies. In conclusion, important features of LC-MS/MS methodology for Alzheimer's drugs include shortened analysis time, increased throughput, selectivity and lower cost of analysis.
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