Non-invasive aerosol delivery and transport of gold nanoparticles to the brain

Ramesh Raliya,Pratim Biswas,Tandeep S Chadha,Baranidharan Raman,Debajit Saha

doi:10.1038/srep44718

Abstract

Targeted delivery of nanoscale carriers containing packaged payloads to the central nervous system has potential use in many diagnostic and therapeutic applications. Moreover, understanding of the bio-interactions of the engineered nanoparticles used for tissue-specific delivery by non-invasive delivery approaches are also of paramount interest. Here, we have examined this issue systematically in a relatively simple invertebrate model using insects. We synthesized 5 nm, positively charged gold nanoparticles (AuNPs) and targeted their delivery using the electrospray aerosol generator. Our results revealed that after the exposure of synthesized aerosol to the insect antenna, AuNPs reached the brain within an hour. Nanoparticle accumulation in the brain increased linearly with the exposure time. Notably, electrophysiological recordings from neurons in the insect brain several hours after exposure did not show any significant alterations in their spontaneous and odor-evoked spiking properties. Taken together, our findings reveal that aerosolized delivery of nanoparticles can be an effective non-invasive approach for delivering nanoparticles to the brain, and also presents an approach to monitor the short-term nano-biointeractions.

Highlights

Targeted delivery of nanoscale carriers containing packaged payloads to the central nervous system has potential use in many diagnostic and therapeutic applications
Once drugs permeate through the nasal epithelium, they transport to the brain along olfactory nerves[16,17]
Since the simplest and shortest path for airborne nanoparticles to reach the central nervous system is through the olfactory tract[18,19,20], intranasal delivery provides the fastest route and potentially a non-invasive option to deliver therapeutic agents to target cells in the brain

Summary

Introduction

Targeted delivery of nanoscale carriers containing packaged payloads to the central nervous system has potential use in many diagnostic and therapeutic applications. Efforts were made to temporarily open the tight blood-brain barrier junctions using either high osmolar solutions[14] or intracerebral injections to cross the BBB15 These invasive approaches have limitations, such as tissue damage, and uncontrolled distribution of the drug from the point of injection. Since the simplest and shortest path for airborne nanoparticles to reach the central nervous system is through the olfactory tract[18,19,20], intranasal delivery provides the fastest route and potentially a non-invasive option to deliver therapeutic agents to target cells in the brain. Our study presents a facile, non-invasive approach for rapid delivery and transport of AuNPs into the brain while minimally disrupting the normal physiology for a limited duration following exposure

Methods

Results

Conclusion