Polymeric nanoparticulate drug delivery through the blood brain barrier

Alzheimer's disease (AD) is the most common cause of dementia among the elderly, affecting 5% of Americans over age 65, and 20% over age 80. An excess of senile plaques (β-amyloid protein) and neurofibrillary tangles (tau protein), ventricular enlargement, and cortical atrophy characterizes it. Unfortunately, targeted drug delivery to the Central Nervous System (CNS), for the therapeutic advancement of neurodegenerative disorders such as Alzheimer's, is complicated by restrictive mechanisms imposed at the blood brain barrier (BBB). Opsonization by plasma proteins in the systemic circulation is an additional impediment to cerebral drug delivery. Here, we attempt to show that biodegradable polymeric nanoparticles (NPs) with appropriate surface modifications can deliver drugs of interest beyond the BBB for diagnostic and therapeutic applications, thus allowing the study of neurological disorders. Particularly, the radiolabelled Cu²⁺ or Fe³⁺ metal chelator Clioquinol (CQ), which has a high affinity for amyloid plaques with a radio-isotope ¹²⁵I, and encapsulated ¹²⁵I-CQ within small, spherical, lipophilic drug carriers are capable of crossing the BBB. In this feature article, the biodistribution patterns of such nanoparticle drug carriers in wild type Swiss Webster mice are compared with free ¹²⁵I-CQ. The physicochemical properties of the NPs at different surfactant concentrations, stabilizers, and amyloid-affinity agents could influence the transport mechanism.