AAAR 35th Annual Conference October 17 - October 21, 2016 Oregon Convention Center Portland, Oregon, USA
Abstract View
Aerosol Based Gold Nanoparticles Delivery to Brain: A Non-Invasive Approach to Cross Blood Brain Barrier
RAMESH RALIYA, Debajit Saha, Tandeep Chadha, Baranidharan Raman, Pratim Biswas, Washington University in St. Louis
Abstract Number: 132 Working Group: Health Related Aerosols
Abstract There is significant interest in the translocation of very small nanoparticles to the brain; with relevance in the field of nanotoxicology and nanomedicine. An emerging field of nanomedicine involves the use of gold nanoparticles both as a diagnostic and/or therapeutic agent. While nanoparticle drug delivery has been used for translocation to a variety of organs, the delivery to the brain has not been extensively validated due to the blood-brain barrier. Conventional approaches such as intravenous injection and intranasal exposure suffer from low efficiency and off target delivery of the particles. To address these challenges, in the present investigation 5 nm gold nanoparticles were synthesized by a novel technique. These were then aerosolized using electro-hydro atomization. Studies involving nanoparticle exposure, accumulation, and bio-interactions were done with locusts (Schistocerca americana), whose olfactory system is functionally and architecturally very similar to the mammalian olfactory system.
In this work, our first goal was to quantify uptake and translocation of custom-designed nanoparticles to the brain through the olfactory sensory pathway. Insect antenna, sensory appendage at the periphery of the olfactory pathway, was exposed to the gold nanoparticles by using electrospray aerosol technique. Transport and accumulation of gold nanoparticles in the olfactory pathway were studied by fluorescence microscopy, transmission electron microscopy, and quantitatively by inductively coupled plasma mass spectroscopy. As a result of aerosol exposure to locust antenna, gold nanoparticles were observed to translocate to the brain in an hour. Quantitatively, gold was detected in the range of 5 and 19 µg from the exposed locusts’ brains during the exposure period of 1 and 6 hours.
Our second goal was to identify the interactions of the translocated nanoparticles with the brain physiology. To achieve this goal, electrophysiological changes in the olfactory neurons due to nanoparticle interactions were studied by multi-electrode extracellular recording technique. We found that principle neurons in the antennal lobe (similar to the olfactory bulb in vertebrates) did not show any significant changes in their passive or active firing properties due to interactions with the gold nanoparticles that were transported to the brain through antennal exposure.
Overall, our findings suggest that by combining electrospray aerosol technique and custom-designed minimally-interactive gold nanoparticles, pharmacokinetically significant amount of nanoscale drug (or drug loaded in such nanoscale carrier) could potentially be delivered to the brain. To the best of our knowledge, this is the first holistic report for the aerosol delivery of gold nanoparticles and study of its interactions with the brain.