Targeting Pharmacons to the Brain via the Nasal Pathway

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...

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...

Journal of controlled release : official journal of the Controlled Release Society, 2014

The blood-brain barrier (BBB) prevents drugs' permeability into the brain and limits the management of brain diseases. Intranasal delivery is a convenient route of drug administration that can bypass the BBB and lead to a direct delivery of the drug to the brain. Indeed, drug accumulation in the brain following intranasal application of a drug solution, or of a drug encapsulated in specialized delivery systems (DDSs), has been reported in numerous scientific publications. We aimed to analyze the available quantitative data on drug delivery to the brain via the nasal route and to reveal the efficiency of brain drug delivery and targeting by different types of nasally-administered DDSs. We searched for scientific publications published in 1970-2014 that reported delivery of drugs or model compounds to the brain via intranasal and parenteral routes, and contained quantitative data that were sufficient for calculation of brain targeting efficiency. We identified 73 publications (tha...

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...

Current Drug Therapy, 2018

Brain targeting has always been challenging due to the presence of various physiological barriers resulting in low bioavailability via the oral and parenteral route. Altering the integrity of these barriers so as to permit the drugs to enter into the brain could severely damage the Central Nervous System by also allowing the entrance of toxic substances, bacteria and viruses into the brain. This problem can be tackled by delivering drugs via the intranasal route which bypasses the blood brain barrier and reaches different parts of the brain primarily via the olfactory and trigeminal neural pathways. This route offers several advantages over the oral and parenteral route and has shown potential for targeting drugs to the brain for treating various central nervous system disorders such as Psychosis, Parkinson's and Alzheimer's disease. In spite of several advantages, the intranasal route faces many challenges. Hence, a complete understanding of every aspect related to nose to brain delivery is of utmost importance. This article reviews the mechanism of nose to brain drug transport, challenges and approaches for nose to brain drug delivery, a few specialized olfactory delivery devices and some applications of this novel route of brain targeting.

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.

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.

Brain Research Bulletin, 2018

The acute or chronic drug treatments for different neurodegenerative and psychiatric disorders are challenging from several aspects. The low bioavailability and limited brain exposure of oral drugs, the rapid metabolism, elimination, the unwanted side effects and also the high dose to be added mean both inconvenience for the patients and high costs for the patients, their family and the society. The reason of low brain penetration of the compounds is that they have to overcome the blood-brain barrier which protects the brain against xenobiotics. Intranasal drug administration is one of the promising options to bypass blood-brain barrier, to reduce the systemic adverse effects of the drugs and to lower the doses to be administered. Furthermore, the drugs administered using nasal route have usually higher bioavailability, less side effects and result in higher brain exposure at similar dosage than the oral drugs. In this review the focus is on giving an overview on the anatomical and cellular structure of nasal cavity and absorption surface. It presents some possibilities to enhance the drug penetration through the nasal barrier and summarizes some in vitro, ex vivo and in vivo technologies to test the drug delivery across the nasal epithelium into the brain. Finally, the authors give a critical evaluation of the nasal route of administration showing its main advantages and limitations of this delivery route for CNS drug targeting.

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.