Functionalized Nanoparticles in Drug Delivery: Strategies to Enhance Direct Nose-to-Brain Drug Delivery via Integrated Nerve Pathways

Abstract

AbstractNose-to-brain drug delivery system is becoming a desirable alternative approach to conventional drug delivery systems used for the treatment of various neurological disorders. Trigeminal and olfactory routes are implicated to deliver drugs from the nose-to-brain, which bypasses the blood-brain barrier and the first-pass metabolism. In this review, nanocarrier systems are evaluated, screened, and tested in order to evaluate its physiochemical features and configuration to enhance the bioavailability of drugs in the brain after intranasal intervention. The application of specific ligand, surface modifications, and use of permeation enhancers to increase brain targeting are discussed. Furthermore, we discuss the in vivo animal and in vitro cell line-based models, which are actively being employed to explore the nanomaterial-driven drug transport mechanisms via the intranasal route. These models can be used to study absorption, diffusion, permeation, and toxicological and pharmacokinetic profile of the active pharmaceutical ingredient. Our review provides evidence to conclude that the potential of nose-to-brain delivery and role of functionalization of nanomaterials enhance the drug efficacy in brain diseases. We also conclude that the biorecognitive surface modifiers have the ability to enhance and optimize the drug delivery to the brain, and we provided our insights and outlooks to address challenges and opportunities for nanosystems to speed up clinical translation.KeywordsNose-to-brainNanomaterialsNerve pathwaysBioavailabilityNeurological disorders