Advances in Drug Delivery from Nose to Brain: An Overview

Introduction: The blood--brain barrier (BBB) represents a stringent barrier for delivery of neurotherapeutics in vivo. An attempt to overcome this barrier is represented by the direct transport of drugs from the nose to the brain along the olfactory and trigeminal nerve pathways. These nerve pathways initiate in the nasal cavity at olfactory neuroepithelium and terminate in the brain. An enormous range of neurotherapeutics, both macromolecules and low molecular weight drugs, can be delivered to the central nervous system (CNS) via this route. Areas covered: Present review highlights the literature on the anatomyphysiology of the nasal cavity, pathways and mechanisms of neurotherapeutic transport across nasal epithelium and their biofate and various strategies to enhance direct nose to brain drug delivery. The authors also emphasize a variety of drug molecules and carrier systems delivered via this route for treating CNS disorders. Patents related to direct nose to brain drug delivery systems have also been listed. Expert opinion: Direct nose to brain drug delivery system is a practical, safe, non-invasive and convenient form of formulation strategy and could be viewed as an excellent alternative approach to conventional dosage forms. Existence of a direct transport route from the nasal cavity to the brain, bypassing the BBB, would offer an exciting mode of delivering neurotherapeutic agents.

Curr Pharm Biotechnol, 2012

The treatment of brain disorders is particularly challenging due to the presence of a variety of formidable obstacles to deliver drugs selectively and effectively to the brain. Blood-brain-barrier (BBB) constitutes the major obstacle to the uptake of drugs into the brain following systemic administration. Intranasal delivery offers a non-invasive and convenient method to bypass the BBB and delivery of therapeutics directly to the brain. The review discusses the potential of intranasal route to deliver drugs to the brain, the mechanisms and pathways of direct nose to brain drug transport, the various factors influencing transnasal drug absorption, the conventional and novel intranasal drug delivery systems, the various intranasal drug delivery techniques and devices, and examples of brain drug transport that have been feasible in treating various brain disorders. Moreover, products on the market, investigational drugs, and the author's perceptions about the prospect of intranasal delivery for treating brain disorders are also been discussed.

Present review highlights the potential of nasal mucosa as an administration route for targeting the central nervous system, the brain. Targeted drug delivery seeks to concentrate the medication in the tissues of interest while reducing the relative concentration of medication in the remaining tissues. Thus improving efficacy of the drug and reducing side effects. The nasal mucosa when compared to other mucous membranes is easily accessible and provides a practical entrance portal for small and large molecules. Intranasal administration offers rapid onset of action, no first-pass effect, no gastrointestinal degradation or lung toxicity and non-invasiveness application and also improves bioavailability. It is thought that olfactory route of drug transport, by pass the blood-brain barrier and allows the direct transport of drug from the nose to the brain. This review provides an overview of strategies to improve the drug delivery to brain via nasal mucosa and recent advances in this f...

Research Journal of Pharmaceutical Dosage Forms and Technology, 2021

The treatment of brain disorders is particularly challenging due to the presence of a variety of formidable obstacles to deliver drugs selectively and effectively to the brain. Blood-brain-barrier (BBB) constitutes the major obstacle to the uptake of drugs into the brain following systemic administration. An intranasal delivery provides some drugs with short channels to bypass the blood-brain barrier (BBB), especially for those with fairly low brain concentrations after a routine delivery, thus greatly enhancing the therapeutic effect on brain diseases. The nasal mucosa is nearby the brain, cerebrospinal fluid (CSF) and the drug concentrations can exceed plasma concentrations. a longer retention time at the nasal mucosal surface, penetration enhancement of the active through the nasal epithelia, and a reduction in drug metabolism in the nasal cavity. Indications where nose-to-brain products are likely to emerge first include the following: neurodegeneration, post-traumatic stress di...

Journal of Controlled Release, 2017

The blood-brain barrier (BBB) restricts the transport of potential therapeutic moieties to the brain. Direct targeting the brain via olfactory and trigeminal neural pathways by passing the BBB has gained an important consideration for delivery of wide range of therapeutics to brain. Intranasal route of transportation directly delivers the drugs to brain without systemic absorption, thus avoiding the side effects and enhancing the efficacy of neurotherapeutics. Over the last several decades, different drug delivery systems (DDSs) have been studied for targeting the brain by the nasal route. Novel DDSs such as nanoparticles (NPs), liposomes and polymeric micelles have gained potential as useful tools for targeting the brain without toxicity in nasal mucosa and central nervous system (CNS). Complex geometry of the nasal cavity presented a big challenge to effective delivery of drugs beyond the nasal valve. Recently, pharmaceutical fir ms utilized latest and emerging nasal drug delivery technologies to overcome these barriers. This review aims to describe the latest development of brain targeted DDSs via nasal administration.

2020

Use of the nasal route for the delivery of challenging drugs such as small polar molecules, vaccines, hormones, peptides and proteins has created much interest in nowadays. Due to the high permeability, high vasculature, low benzymatic environment of nasal cavity and avoidance of hepatic first pass metabolism are well suitable for systemic delivery of drug molecule via nose. The unique relationship between nasal cavity and cranial cavity tissues in anatomy and physiology makes intranasal delivery to the brain feasible. An intranasal delivery provides some drugs with short channels to bypass the blood–brain barrier (BBB), especially for those with fairly low brain concentrations after a routine delivery, thus greatly enhancing the therapeutic effect on brain diseases. In the past two decades, a good number of encouraging outcomes have been reported in the treatment of diseases of the brain or central nervous system (CNS) through nasal the paper also includes. The different types of b...

Zenodo (CERN European Organization for Nuclear Research), 2021

The goal of brain drug targeting technology is the delivery of therapeutics across the blood brain barrier (BBB), including the human BBB. Nose to brain drug delivery has received a great deal of attention as a non-invasive, convenient and reliable drug delivery system. For the systemic and targetedadministration of drug. The various drug deliveries through some drug transport pathways, Factor influencing nasal drug absorption, formulation strategies nose to brain, colloidal carriers in nose to brain drug delivery system and nasal delivery systems. Physiological barriers (BBB) that restricts the delivery of drug to CNS. Thus intranasal route has attracted a wide attention of convenient, noninvasive, reliable, and safe route to achieve faster and higher level of drug in the brain through olfactory region by passing blood brain barrier. Intranasal administration rapid onset of action, no first-pass effect , no gastrointestinal degradation lungs toxicity and non-invasiveness application and also improves bioavailability.

Therapeutic Delivery, 2014

The intricate pathophysiology of brain disorders, difficult access to the brain, and the complexity and high risks and costs of drug development represent major hurdles for improving therapies. Nose-to-brain drug transport offers an attractive alternative or addition to formulation-only strategies attempting to enhance drug penetration into the CNS. Although still a matter of controversy, many studies in animals claim direct nose-to-brain transport along the olfactory and trigeminal nerves, circumventing the traditional barriers to CNS entry. Some clinical trials in man also suggest nose-to-brain drug delivery, although definitive proof in man is lacking. This review focuses on new nasal delivery technologies designed to overcome inherent anatomical and physiological challenges and facilitate more efficient and targeted drug delivery for CNS disorders.

Journal of controlled release : official journal of the Controlled Release Society, 2018

According to the Alzheimer Association Report (2017), Alzheimer's disease (AD) is the 6th primary cause of death in the USA, which affects nearly 5.5 million people. In the year 2017 itself, the cost of AD treatment in the USA has been reported to rise to $259 billion. This statistic shows the severity of the disease in the USA which is very much similar across the globe. On the other hand, the treatment remains limited to a few conventional oral medications (approved by FDA). These are mainly acting superficially from mild to the moderate AD. The therapeutic efficacy of the drug is not only affected by its reduced concentration in the brain owing to the existence of blood-brain-barrier (BBB) but also due to its low brain permeability. In this context, the intranasal (IN) route of drug administration has emerged as an alternative route over the systemic (oral and parenteral) drug delivery to the brain. The delivery of the drug via an IN route offers various advantages over syste...

Present review highlights the potential of nasal mucosa as an administration route for targeting the central nervous system (CNS), in particular, the brain. Delivery of drugs to the brain is a most formidable challenge in current scenario due to presence of physiological barriers that restricts the delivery of drugs to CNS. Thus, since last few decades, nasal route has attracted a wide attention of researchers as a convenient, non-invasive, reliable, and safe route to achieve faster and higher levels of drug in the brain. It is thought to do so through olfactory route of drug transport which bypass the blood-brain barrier (BBB) and allow the direct transport of drug from the nose to the brain. Herein, authors had tried to highlight the prominent aspects and key findings relevant to drug delivery systems for targeting the brain via nasal route of drug administration. Anatomy and physiology of nose, key benefits offered by nasal drug delivery systems, mechanisms of drug absorption across nasal mucosa and metabolism of drugs in nasal cavity are discussed in sufficient depth. Various formulation strategies for enhanced nose to brain drug delivery and various colloidal carriers for brain targeted drug delivery are discussed to their extreme. Rising needs of controlled and site specific drug delivery systems accounts for the use of colloidal nanocarriers and has became a revolutionary approach. Colloidal carriers are at forefront of the rapidly expanding field of nanotechnology with numerous potential applications in drug delivery, clinical medicines and scientific research. The success of nanocarriers for targeted drug delivery depends on their ability to incorporate drugs of different kinds of therapeutic agents, penetrate through several anatomical barriers, sustained release of incorporated drugs, and stability in nanometric size range. Such characteristics of nanocarriers offer a new breakthrough in drug delivery and therapeutics that holds great promise for achieving the goal of controlled and site-specific drug delivery.