Recent advances in carrier mediated nose-to-brain delivery of pharmaceutics

Abstract

Central nervous system (CNS) disorders (e.g., multiple sclerosis, Alzheimer's disease, etc.) represent a growing public health issue, primarily due to the increased life expectancy and the aging population. The treatment of such disorders is notably elaborate and requires the delivery of therapeutics to the brain in appropriate amounts to elicit a pharmacological response. However, despite the major advances both in neuroscience and drug delivery research, the administration of drugs to the CNS still remains elusive. It is commonly accepted that effectiveness-related issues arise due to the inability of parenterally administered macromolecules to cross the Blood-Brain Barrier (BBB) in order to access the CNS, thus impeding their successful delivery to brain tissues. As a result, the direct Nose-to-Brain delivery has emerged as a powerful strategy to circumvent the BBB and deliver drugs to the brain. The present review article attempts to highlight the different experimental and computational approaches pursued so far to attain and enhance the direct delivery of therapeutic agents to the brain and shed some light on the underlying mechanisms involved in the pathogenesis and treatment of neurological disorders.

The Hypotonic Environmental Changes Affect Liposomal Formulations for Nose-to-Brain Targeted Drug Delivery

“…One of the most promising routes of administration appears to be the nose-to-brain targeted drug administration. 5,6 The nasal epithelium is divided into the olfactory and respiratory region. [5][6][7] Drugs that are absorbed through the olfactory region have the potential to avoid systemic elimination (i.e.…”

“…), reach the cerebrospinal fluid (CSF) and accumulate in the brain bypassing the BBB. [5][6][7][8] This route of drug administration is unfortunately limited by low absorption through the olfactory epithelium because of the limited surface area, early enzymatic degradation and rapid ciliary clearance. 9 However, new research has shown that liposomes can optimize nose-to-brain targeted drug delivery.…”

“…(5) (adaptation of Fick's first law) can describe the permeability of a drug through a regenerated cellulose barrier as; the diffusion coefficient and dc/dx the gradient of concentration between donor and acceptor compartment. From this equation it is evident that, normalizing the concentration and assuming same thickness of the barrier in all experiments, the differences in permeability (and therefore in resistance to transport) within different drugs through cellulose barriers are solely given by the different diffusion coefficients of each drug.…”

Trimethyl Chitosan Hydrogel Nanoparticles for Progesterone Delivery in Neurodegenerative Disorders

“…Drug administered by this route can enter the brain principally using olfactory or trigeminal nerve pathways. Moreover, other pathways involving vasculature, cerebrospinal fluid, and the lymphatic system have been individuated [17,18].…”

A CGRP receptor antagonist peptide formulated for nasal administration to treat migraine

“…[33] Recent developments in the delivery of drugs to the brain, including the use of delivery vehicles such as microand nano-carriers alongside mucoadhesive agents such as chitosan, are promising. [19] In this study, we have investigated the antagonist properties of a synthetic N-terminally truncated and modified human CGRP peptide. We show that ( 34 Pro, 35 Phe) CGRP 27-37 is a potent CGRP receptor antagonist both in vitro and, for the first time, in vivo and demonstrate how it can be formulated for dry powder nasal delivery without loss of potency.…”