Non-Invasive Techniques of Nose to Brain Delivery Using Nanoparticulate Carriers: Hopes and Hurdles

Intranasal drug delivery route has emerged as a promising non-invasive method of administering drugs directly to the brain, bypassing the blood-brain barrier (BBB) and blood-cerebrospinal fluid barriers (BCSF). BBB and BCSF prevent many therapeutic molecules from entering the brain. Intranasal drug delivery can transport drugs from the nasal mucosa to the brain, to treat a variety of Central nervous system (CNS) diseases. Intranasal drug delivery provides advantages over invasive drug delivery techniques such as intrathecal or intraparenchymal which can cause infection. Many strategies, including nanocarriers liposomes, solid-lipid NPs, nano-emulsion, nanostructured lipid carriers, dendrimers, exosomes, metal NPs, nano micelles, and quantum dots, are effective in nose-to-brain drug transport. However, the biggest obstacles to the nose-to-brain delivery of drugs include mucociliary clearance, poor drug retention, enzymatic degradation, poor permeability, bioavailability, and naso-mucosal toxicity. The current review aims to compile current approaches for drug delivery to the CNS via the nose, focusing on nanotherapeutics and nasal devices. Along with a brief overview of the related pathways or mechanisms, it also covers the advantages of nasal drug delivery as a potential method of drug administration. It also offers several possibilities to improve drug penetration across the nasal barrier. This article overviews various in-vitro, ex-vivo, and in-vivo techniques to assess drug transport from the nasal epithelium into the brain.