Nanotechnological Advances for Nose to Brain Delivery of Therapeutics to Improve the Parkinson Therapy

Abstract

Blood-Brain Barrier (BBB) acts as a highly impermeable barrier, presenting an impediment for the crossing of most classical drugs targeted for neurodegenerative diseases including Parkinson's disease (PD). Pertaining to the nature of drugs and other potential molecules, they impose unavoidable dose-restricted limitations eventually leading to the failure of therapy. However, many advancements in formulation technology and maneuvering of delivery approaches have been successful in delivering the drug to the brain in the therapeutic window. The nose to the brain (N2B) drug delivery employing the nano formulation, is one such emerging delivery approach, curbing both classical drug formulation and delivery-associated limitation. Later offers increased bioavailability, greater patient acceptance, less biological interference, circumvention of BBB, ample drug loading along with the controlled release of the drugs. In N2B delivery, the intranasal (IN) route carries therapeutics firstly into the nasal cavity followed by the brain through olfactory & trigeminal nerve connections linked with nasal mucosa. The N2B delivery approach is being explored for delivering other biologicals like neuropeptides and mitochondria. Meanwhile, this N2B delivery system is associated with vital challenges consisting of mucociliary clearance, degradation by enzymes, drug translocations by efflux mechanisms. These challenges finally culminated in the development of suitable surface-modified nano-carriers and ultrasound-assisted IN as FUS-IN technique which really has expanded the horizons of N2B drug delivery. Hence, nanotechnology, in collaboration with advances in the IN route of drug administration, has diversified a new marvel for treating PD. The present review discusses physiology, limitation of IN delivery along with current advances in nano carrier and technical development assisting N2B drug delivery.

Research progress in brain-targeted nasal drug delivery

“…Many enzyme systems catalyze the biological processes occurring within the nasal mucosa; these systems include cytochrome enzyme subunits, epoxidases, polymerases, peptidases, and proteases, all of which can lead to drug degradation in the nasal cavity, producing a “pseudo-first pass effect” that limits the amount of peptide- and protein-based drugs that might otherwise enter the brain ( Oliveira et al, 2016 ). Administration of enzyme inhibitors can reduce the expression or activity of enzymes, thereby increasing drug uptake ( Khatri et al, 2023 ).…”

Nasal Delivery to the Brain: Harnessing Nanoparticles for Effective Drug Transport

“…In general, nanoparticles show great potential in the field of nose-to-brain medication delivery. They are constantly being improved and developed to overcome obstacles and enhance the effective and precise transport of drugs to the brain for the treatment of neurological illnesses [ 68 ]. Various nanoparticles with their characteristics for nose-to-brain drug-delivery systems are described in Table 3 .…”

The Management of Parkinson’s Disease: An Overview of the Current Advancements in Drug Delivery Systems

“…Intranasal administration is another popular route used to deliver micro-/nano-enabled drugs to the CNS, through olfactory and trigeminal pathways [ 102 ]. The intranasal route facilitates bioavailability improvement and dose reduction of therapeutic molecules, owing to its ability to bypass the BBB [ 103 ]. In addition to this, since many PD patients experience dysphagia as their condition worsens, significant work has been put into developing novel formulations of these medicines to treat these conditions, allowing their delivery at lower concentrations ( Table 2 ) (e.g., inhaled L-DOPA).…”