Auricular Route as a Next-Generation Gateway for Nanotherapeutic Delivery: Bioinspired Strategies for the Intervention of Neurodegenerative Disorders
Akash Gupta, Rakesh Tiwle, Irfan Pathan, Arif Raza, Yamini Sahu, Nikita Verma, Sanjay Kumar GuptaIntroduction:
Alzheimer's Disease (AD) and Parkinson's Disease (PD) are progressive in nature and are classified as neurodegenerative diseases. Because treatments are often ineffective and drugs have limited ability to cross the blood-brain barrier (BBB), extensive research has explored the auricular route as a potentially less invasive way to deliver drugs to the CNS and modulate the nervous system locally. Currently, evidence is insufficient to support direct BBB bypass.
Methods:
This study is a narrative review of the evidence supporting the use of auricular therapies, including auricular vagus nerve stimulation (aVNS), localised delivery of drugs via the auricular region, and delivery of therapeutics to the auricular region using nano-carriers, in the treatment of AD and PD. The literature was reviewed for its mechanistic rationale and evidence supporting its use, as well as to identify translational barriers to treatment.
Results:
There is little current literature exploring the auricle for delivering treatments aimed at slowing down the progression of Neurodegenerative Disorders. There is evidence from preclinical and early-phase studies showing that treatments through the auricle may change neuroinflammatory signalling, regulate neurotransmitter activity, and provide controlled pharmacological delivery. Studies on aVNS suggest how it modulates autonomic and inflammatory pathways. Nanocarrier systems may facilitate improved localized pharmacological delivery, but current data supporting pharmacokinetics/biodistribution and clinical outcomes remain scarce.
Conclusion:
Auricular methods of treatment may offer a new method to reduce the invasiveness of treatment options that are given to reduce the progression of both AD and PD, but further mechanistic, translational, and clinical studies remain required to support efficacy.