110th Anniversary: Nanoparticle Mediated Drug Delivery for the Treatment of Alzheimer's Disease: Crossing the Blood-Brain Barrier

Alzheimer's disease is an irreversible neuro-degenerative disorder affecting approximately 6 million Americans, 90% of which are over the age of 65. The hallmarks of the disease are represented by amyloid plaques and neurofibrillary tangles. While the neuronal characteristics of Alzheimer's disease are well-known, current treatments only provide temporary relief of the disease symptoms. Many of the approved therapeutic agents for the management of cognitive impairments associated with the disease are based on neurotransmitter or enzyme modulation. However, development of new treatment strategies is limited due to failures associated with poor drug solubility, low bioavailability, and the inability to overcome obstacles present along the drug delivery route. In addition, treatment technologies must overcome the challenges presented by the blood-brain barrier. This complex and highly regulated barrier surveys the biochemical, physicochemical, and structural features of nearby molecules at the periphery, only permitting passage of select molecules into the brain. To increase drug efficacy to the brain, many nanotechnology-based platforms have been developed. These methods for assisted drug delivery employ sophisticated design strategies and offer serveral advantages over traditional methods. For example, nanoparticles are generally low-cost technologies, which can be used for noninvasive administrations, and formulations are highly tunable to increase drug loading, targeting, and release efficacy. These nanoscale systems can facilitate the passage of drugs through the blood-brain barrier, thus improving the bioavailability, pharmacokinetics, and pharmacodynamics of therapeutic agents. Examples of such nanocarriers that are discussed herein include polymeric nanoparticles, dendrimers, and lipid-based nanoparticles.