Advances and Challenges in Intranasal Delivery of Antipsychotic Agents Targeting the Central Nervous System

Abstract

Treatment of central nervous system (CNS) disorders is challenging using conventional delivery strategies and routes of administration because of the presence of the blood–brain barrier (BBB). This BBB restricts the permeation of most of the therapeutics targeting the brain because of its impervious characteristics. Thus, the challenges of delivering the therapeutic agents across the BBB to the brain overcoming the issue of insufficient entry of neurotherapeutics require immediate attention for recovering from the issues by the use of modern platforms of drug delivery and novel routes of administration. Therefore, the advancement of drug delivery tools and delivering these tools using the intranasal route of drug administration have shown the potential of circumventing the BBB, thereby delivering the therapeutics to the brain at a significant concentration with minimal exposure to systemic circulation. These novel strategies could lead to improved efficacy of antipsychotic agents using several advanced drug delivery tools while delivered via the intranasal route. This review emphasized the present challenges of delivering the neurotherapeutics to the brain using conventional routes of administration and overcoming the issues by exploring the intranasal route of drug administration to deliver the therapeutics circumventing the biological barrier of the brain. An overview of different problems with corresponding solutions in administering therapeutics via the intranasal route with special emphasis on advanced drug delivery systems targeting to deliver CNS therapeutics has been focused. Furthermore, preclinical and clinical advancements on the delivery of antipsychotics using this intranasal route have also been emphasized.

Cataleptogenic Effect of Haloperidol Formulated in Water-Soluble Calixarene-Based Nanoparticles

“…Intranasal administration for the treatment of diseases of the CNS is attractive because it allows the drug to be delivered directly to the brain, bypassing the blood-brain barrier. At the same time, neurotherapeutic drugs are delivered to the brain in significant concentrations with minimal exposure to systemic circulation [ 46 ]. The results of the cataleptogenic effect of Hal in the formulation with VC10, and the commercial formulation of Hal (as a control), with intranasal administration are shown in Figure 8 .…”

Self-Emulsifying Drug Delivery Systems: An Alternative Approach to Improve Brain Bioavailability of Poorly Water-Soluble Drugs through Intranasal Administration

“…It provides advantages such as ease and self-administration, suitability for long-term use, cost effectiveness, and ability for scale-up manufacturing [ 27 , 67 ]. However, after oral administration, drugs need to pass several GIT compartments with different characteristics in terms of pH, aqueous volume, and membrane structures [ 2 ]. In addition, drug solubilization within GIT is mandatory, since incomplete dissolution may lead to incomplete absorption, low bioavailability, and higher fluctuations in systemic concentration [ 9 ].…”

“…Even so, a percentage of the administered dose can reach the systemic circulation. However, due to other physicochemical characteristics such as high molecular weight, these molecules could be restricted in passing through the BBB, hardly achieving effective therapeutic concentrations in the brain [ 2 , 3 ]. Different types of lipidic nanosystems have been developed to overcome the disadvantages of oral administration of neurotherapeutics, SEDDS being one of those systems [ 13 , 22 ].…”

“…In fact, global statistics show that 50 million people suffer from epilepsy, 62 million from cerebrovascular diseases, 326 million from migraine, and 24 million from Alzheimer's disease and other dementias. For that reason, Pharmaceutics 2022, 14, 1487 2 of 28 neurological disorders are considered one of the biggest causes of disability and death worldwide [1,2]. Taking this into account, efforts in discovering and developing new and effective neuropharmaceuticals are made daily, even though most of the new entities fail to reach clinical trials [3].…”

Brain Targeting by Intranasal Drug Delivery: Effect of Different Formulations of the Biflavone “Cupressuflavone” from Juniperus sabina L. on the Motor Activity of Rats

“…A billion people worldwide may suffer from neurological illnesses, according to a 2020 World Health Organization (WHO) assessment [ 1 ]. Based on this fact, neurological illnesses are regarded as one of the leading causes of disability and fatalities globally [ 1 , 2 ]. Despite the fact that the majority of novel entities never make it to clinical trials, scientific efforts are continuous to find and create new and effective neuropharmaceuticals.…”