Recent Strategies for Targeted Brain Drug Delivery

Abstract

Because the brain is the most important human organ, many brain disorders can cause severe symptoms. For example, glioma, one type of brain tumor, is progressive and lethal, while neurodegenerative diseases cause severe disability. Nevertheless, medical treatment for brain diseases remains unsatisfactory, and therefore innovative therapies are desired. However, the development of therapies to treat some cerebral diseases is difficult because the blood-brain barrier (BBB) or blood-brain tumor barrier prevents drugs from entering the brain. Hence, drug delivery system (DDS) strategies are required to deliver therapeutic agents to the brain. Recently, brain-targeted DDS have been developed, which increases the quality of therapy for cerebral disorders. This review gives an overview of recent brain-targeting DDS strategies. First, it describes strategies to cross the BBB. This includes BBB-crossing ligand modification or temporal BBB permeabilization. Strategies to avoid the BBB using local administration are also summarized. Intrabrain drug distribution is a crucial factor that directly determines the therapeutic effect, and thus it is important to evaluate drug distribution using optimal methods. We introduce some methods for evaluating drug distribution in the brain. Finally, applications of brain-targeted DDS for the treatment of brain tumors, Alzheimer's disease, Parkinson's disease, and stroke are explained.

Cellular Trafficking of Nanotechnology‐Mediated mRNA Delivery

“…For instance, microbubbleassisted focused ultrasound (FUS) has shown potential in triggering temporary BBB opening and enabling systemic delivery of LNP/mRNA formulations to the brain with enhanced exogenous protein production across the BBB. [178,179]…”

Dietary Plant Polyphenols as the Potential Drugs in Neurodegenerative Diseases: Current Evidence, Advances, and Opportunities

“…Therefore, the BBB has important biological significance for maintaining the basic stability of the internal environment of brain tissues and the normal physiological state of the CNS [385]. However, the presence of the BBB severely prevents most drugs such as many polyphenols from entering the brain to exert their effects [386]. Although a large number of studies have shown that some plant polyphenols can cross the BBB and reach the brain to exert a neuroprotective effect, there are still many polyphenols reported having indirect beneficial effects in neurodegenerative diseases [387][388][389].…”

A trip of peptides to the brain

“…Thus, in situ perfusion experiments provide in vivo evidence on possible transportability of peptides in intact form across the BBB. The criteria for the selection of BBB transporting peptides is (1) a dipeptide skeleton [because transporters related to influx transport direction recognize small nutrients such as glucose and amino acids (Ogawa et al 2020)], (2) PHT-1 substrate or dipeptides recognized by PHT1, which is abundantly expressed in the nerve system (Yamashita et al 1997), and (3) hydrophobicity that may assist the transcellular diffusive transport (Nau et al 1994). According to the criteria, the uptake (brain/perfusate ratio, μL/g-brain) of dipeptides listed in Table 2 is evaluated in in situ 2.0-min mouse perfusion experiments (Tanaka et al 2019).…”

“…The BBB regulates or limits compounds acceptable for the brain, including amino acids, glucose, organic/inorganic compounds, and vitamins, whereas large compounds fail the BBB transport (Ogawa et al 2020). Thus, transporters capable of recognizing and transporting nutrients are individually expressed at luminal and abluminal sides of the BBB; typical influx (blood to brain direction) transporters are glucose transporter 1 (GLUT1) for glucose, large neutral amino acid transporter 1 (LAT1), and monocarboxylate transporter 1 (MCT1).…”