Brain Targeting Drug Delivery System Research Articles

Advancements in strategies for overcoming the blood-brain barrier to deliver brain-targeted drugs.

The blood-brain barrier is known to consist of a variety of cells and complex inter-cellular junctions that protect the vulnerable brain from neurotoxic compounds; however, it also complicates the pharmacological treatment of central nervous system disorders as most drugs are unable to penetrate the blood-brain barrier on the basis of their own structural properties. This dramatically diminished the therapeutic effect of the drug and compromised its biosafety. In response, a number of drugs are often delivered to brain lesions in invasive ways that bypass the obstruction of the blood-brain barrier, such as subdural administration, intrathecal administration, and convection-enhanced delivery. Nevertheless, these intrusive strategies introduce the risk of brain injury, limiting their clinical application. In recent years, the intensive development of nanomaterials science and the interdisciplinary convergence of medical engineering have brought light to the penetration of the blood-brain barrier for brain-targeted drugs. In this paper, we extensively discuss the limitations of the blood-brain barrier on drug delivery and non-invasive brain-targeted strategies such as nanomedicine and blood-brain barrier disruption. In the meantime, we analyze their strengths and limitations and provide outlooks on the further development of brain-targeted drug delivery systems.

Polyamidoamine Dendrimers: Brain-Targeted Drug Delivery Systems in Glioma Therapy.

Glioma is the most common primary intracranial tumor, which is formed by the malignant transformation of glial cells in the brain and spinal cord. It has the characteristics of high incidence, high recurrence rate, high mortality and low cure rate. The treatments for glioma include surgical removal, chemotherapy and radiotherapy. Due to the obstruction of the biological barrier of brain tissue, it is difficult to achieve the desired therapeutic effects. To address the limitations imposed by the brain's natural barriers and enhance the treatment efficacy, researchers have effectively used brain-targeted drug delivery systems (DDSs) in glioma therapy. Polyamidoamine (PAMAM) dendrimers, as branched macromolecular architectures, represent promising candidates for studies in glioma therapy. This review focuses on PAMAM-based DDSs in the treatment of glioma, highlighting their physicochemical characteristics, structural properties as well as an overview of the toxicity and safety profiles.

Boosting physical performance in SD rats through brain-targeted delivery of caffeine-loaded transferrin liposomes

This study aimed to explore the impact of caffeine (CAF) encapsulated in transferrin-modified, sterically-stabilized liposomes (Tf-SSL) on the physical performance of rats, specifically forelimb grip strength, running, and swimming. The brain-targeted drug delivery system, Tf-SSL, was used for the administration of caffeine. 168 male Sprague-Dawley (SD) rats were randomly assigned to different groups, including swimming, running, running wheel, and strength groups. Each group was further subdivided into high, medium, and low dose free caffeine (HCAF, MCAF, LCAF) and Tf-SSL CAF groups, along with a control group (CON). The strength, swimming, and running groups underwent training for four weeks, three times per week. The running wheel group was placed in rearing cages for a one-week adaptation period. After the final training session, the resistance, swimming, running, and running wheel exercise capacities of the rats were tested. The rats were administered treatment via tail vein injection, while the blank CON group received 0.9 % saline solution without treatment throughout the entire process. The results demonstrated a Tf-SSL CAF group encapsulation rate of 70.58 ± 5.14 %. Increasing the concentration of supplemented caffeine led to enhanced forelimb grip strength in rats, with significant differences observed in HCAF alone group, medium-dose Tf-SSL CAF (MTf-SSL CAF), and high-dose Tf-SSL CAF (HTf-SSL CAF) groups compared to the CON group. In the running and swimming experiments, higher caffeine supplementation concentrations correlated with increased running and swimming time to exhaustion, and the MTf-SSL CAF group showed longer running and swimming time compared to the HCAF alone group. The results of rat striatal dopamine levels indicated that increased caffeine supplementation concentrations led to higher dopamine secretion, with significantly different striatal concentrations in the HCAF group, MTf-SSL CAF group, and HTf-SSL CAF group compared to the CON group. The running wheel experiment revealed that rats in the medium- and high-dose Tf-SSL CAF groups exhibited greater 6-h running distances than the HCAF group and CON group. In conclusion, caffeine supplementation improved the physical performance of rats, with the high concentration CAF group outperforming the low and medium concentration groups. Furthermore, Tf-SSL CAF demonstrated superior physical enhancement compared to caffeine supplementation alone.

Enhanced brain-targeting and efficacy of cannabidiol via RVG-Exo/CBD nanodelivery system

This study introduces an innovative brain-targeted drug delivery system, RVG-Exo/CBD, utilizing rabies virus glycoprotein (RVG)-engineered exosomes for encapsulating cannabidiol (CBD). The novel delivery system was meticulously characterized, confirming the maintenance of exosomal integrity, size, and successful drug encapsulation with a high drug loading rate of 83.0 %. Evaluation of the RVG-Exo/CBD's brain-targeting capability demonstrated superior distribution and retention in brain tissue compared to unmodified exosomes, primarily validated through in vivo fluorescence imaging. The efficacy of this delivery system was assessed using a behavioral sensitization model in mice, where RVG-Exo/CBD notably suppressed methamphetamine-induced hyperactivity more effectively than CBD alone, indicating a reduction in effective dose and enhanced bioavailability. Overall, the RVG-Exo/CBD system emerges as a promising strategy for enhancing the therapeutic efficacy and safety of CBD, particularly for neurological applications, highlighting its potential for addressing the limitations associated with traditional CBD administration in clinical settings.

Brain Targeted Drug Delivery System for Microglial Diseases: Recent Developments in Neuroinflammation and Neurodegeneration

Brain Targeted Drug Delivery System for Microglial Diseases: Recent Developments in Neuroinflammation and Neurodegeneration

Brain Targeted Drug Delivery System of Carmustine: Design, Development, Characterization, in vitro, ex vivo Evaluation and in vivo Pharmacokinetic Study

The treatment of gliomas remains difficult task. Carmustine is a drug that is used in the treatment of gliomas. Flexible liposomes embedded in situ thermoreversible nasal gel preparations of Carmustine were studied for in vitro carmustine release, ex vivo carmustine permeation and carmustine release kinetics. The epithelial layers of nasal tissue were found to be intact and undamaged during histological analysis. Intranasal administration of optimized flexible liposomes embedded in a nasal gel showed higher Cmax (Approximately two-fold), AUC0→t (Approximately three-fold), AUC0→∞ (Approximately six-fold), and lower Tmax (1 h) in the brain, compared to intravenous injection of carmustine. The present study demonstrates that the flexible liposome embedded thermoreversible in situ intranasal gel of carmustine improved the targeted uptake of carmustine in the brain through the nasal delivery system and could be a reliable and effective delivery system for carmustine in the treatment of gliomas.

Brain-Wide Transgene Expression in Mice by Systemic Injection of Genetically Engineered Exosomes: CAP-Exosomes.

The bottleneck in drug discovery for central nervous system diseases is the absence of effective systemic drug delivery technology for delivering therapeutic drugs into the brain. Despite the advances in the technology used in drug discovery, such as Adeno-Associated Virus (AAV) vectors, the development of drugs for central nervous system diseases remains challenging. In this manuscript, we describe, for the first time, the development of a workflow to generate a novel brain-targeted drug delivery system that involves the generation of genetically engineered exosomes by first selecting various functional AAV capsid-specific peptides (collectively called CAPs) known to be involved in brain-targeted high-expression gene delivery, and then expressing the CAPs in frame with lysosome-associated membrane glycoprotein (Lamp2b) followed by expressing CAP-Lamp2b fusion protein on the surface of mesenchymal stem cell-derived exosomes, thus generating CAP-exosomes. Intravenous injection of green fluorescent protein (GFP) gene-loaded CAP-exosomes in mice transferred the GFP gene throughout the CNS as measured by monitoring brain sections for GFP expression with confocal microscopy. GFP gene transfer efficiency was at least 20-fold greater than that of the control Lamp2b-exosomes, and GFP gene transduction to mouse liver was low.

Dual fluorescence images, transport pathway, and blood–brain barrier penetration of B-Met-W/O/W SE

Borneol is an aromatic traditional Chinese medicine that can improve the permeability of the blood–brain barrier (BBB), enter the brain, and promote the brain tissue distribution of many other drugs. In our previous study, borneol-metformin hydrochloride water/oil/water composite submicron emulsion (B-Met-W/O/W SE) was prepared using borneol and SE to promote BBB penetration, which significantly increased the brain distribution of Met. However, the dynamic images, transport pathway (uptake and efflux), promotion of BBB permeability, and mechanisms of B-Met-W/O/W SE before and after entering cells have not been clarified. In this study, rhodamine B and coumarin-6 were selected as water-soluble and oil-soluble fluorescent probes to prepare B-Met-W/O/W dual-fluorescent SE (B-Met-W/O/W DFSE) with concentric circle imaging. B-Met-W/O/W SE can be well taken up by brain microvascular endothelial cells (BMECs). The addition of three inhibitors (chlorpromazine hydrochloride, methyl-β-cyclodextrin, and amiloride hydrochloride) indicated that its main pathway may be clathrin-mediated and fossa protein-mediated endocytosis. Meanwhile, B-Met-W/O/W SE was obviously shown to inhibit the efflux of BMECs. Next, BMECs were cultured in the Transwell chamber to establish a BBB model, and Western blot was employed to detect the protein expressions of Occludin, Zona Occludens 1 (ZO-1), and p-glycoprotein (P-gp) after B-Met-W/O/W SE treatment. The results showed that B-Met-W/O/W SE significantly down-regulated the expression of Occludin, ZO-1, and P-gp, which increased the permeability of BBB, promoted drug entry into the brain through BBB, and inhibited BBB efflux. Furthermore, 11 differentially expressed genes (DEGs) and 7 related signaling pathways in BMECs treated with B-W/O/W SE were detected by transcriptome sequencing and verified by quantitative real-time polymerase chain reaction (qRT-PCR). These results provide a scientific experimental basis for the dynamic monitoring, transmembrane transport mode, and permeation-promoting mechanism of B-Met-W/O/W SE as a new brain-targeting drug delivery system.

Research progress in brain-targeted nasal drug delivery.

The unique anatomical and physiological connections between the nasal cavity and brain provide a pathway for bypassing the blood-brain barrier to allow for direct brain-targeted drug delivery through nasal administration. There are several advantages of nasal administration compared with other routes; for example, the first-pass effect that leads to the metabolism of orally administered drugs can be bypassed, and the poor compliance associated with injections can be minimized. Nasal administration can also help maximize brain-targeted drug delivery, allowing for high pharmacological activity at lower drug dosages, thereby minimizing the likelihood of adverse effects and providing a highly promising drug delivery pathway for the treatment of central nervous system diseases. The aim of this review article was to briefly describe the physiological structures of the nasal cavity and brain, the pathways through which drugs can enter the brain through the nose, the factors affecting brain-targeted nasal drug delivery, methods to improve brain-targeted nasal drug delivery systems through the application of related biomaterials, common experimental methods used in intranasal drug delivery research, and the current limitations of such approaches, providing a solid foundation for further in-depth research on intranasal brain-targeted drug delivery systems (see Graphical Abstract).

An Overview of Various Approaches for Brain Targeted Drug Delivery System

The blood-brain barrier (BBB) protects the central nervous system, one of the body’s most fragile microenvironments, by controlling its homeostasis. The BBB is a very complex system that strictly restricts the transport of ions from the blood to the brain of a confined amount of tiny molecules and a much lower number of large molecules, defending the brain from diseases and injuries. However, the BBB severely inhibits drug transport to the brain, hindering the treatment of various neurological problems. As a result, numerous techniques are under development to improve drug delivery across the BBB. This review summarizes the anatomical and physiological characteristics of the barriers and the current drug delivery strategies for the brain. Although these methods provide many fascinating possibilities for targeting and brain delivery, only a few have progressed to the point where they can be used safely and effectively in humans. In addition, concerted efforts using a variety of other methodologies will enable the translation of preclinical findings into tangible clinical applications in the targeted delivery of drugs.

Study on the Nasal Drug Delivery System of NMD Liposomes In Situ Thermosensitive Gel.

Nimodipine (NMD) is a 1,4-dihydropyridine calcium antagonist that is effective in the prevention and treatment of cerebral arterial vasospasm and cerebral ischemic injury caused by subarachnoid hemorrhage. Since the drug itself is highly insoluble in water and has low oral bioavailability, while injectable formulations may cause pain and inflammation, the blood-brain barrier (BBB) prevents the effective delivery of therapeutic agents to the brain tissue. Therefore, in the present study, NMD liposomes were prepared by ethanol injection and innovatively lyophilised and loaded into temperature-sensitive in situ gels for intranasal administration as sprays to deliver drugs to brain tissues bypassing the blood-brain barrier. The optimal gel formulation was obtained by screening in which liposomes were divided into lecithin, cholesterol, and NMD in the ratio of 40:10: 1; Pluronic P407, Pluronic P188, Tween 80, polyvinyl ketone and ethyl nipagin in the ratio of (180:20:3:1:1); Pluronic P407, Pluronic P188, Tween 80, polyvinyl ketone, and ethyl nipagin in the ratio of (180:20:3:1:1). The prepared flow gel can form a solidified gel after a temperature of 31.07-32.07°C and a time of 58.51-59.89s. Meanwhile, the NMD liposome gel formulation achieved sustained release over 56h. The pharmacokinetic results of the developed NMD liposomal temperature-sensitive in situ gel and NMD temperature-sensitive in situ gel showed that liposomal nasal mucosal in situ gel is a more effective brain-targeted drug delivery system for NMD.

Borneol-modified PEGylated graphene oxide as a nanocarrier for brain-targeted delivery of ginsenoside Rg1 against depression

Depression is a chronic mental disorder which threatens human health and lives. However, the treatment of depression remains challenging largely due to blood brain barrier (BBB), which restricts drugs from entering the brain, resulting in a poor distribution of antidepressants in the brain. In this work, a novel brain-targeted drug delivery system was developed based on borneol-modified PEGylated graphene oxide (GO-PEG-BO). GO-PEG-BO was characterized and proved to possess excellent biocompatibility. By incorporating borneol, GO-PEG-BO could penetrate BBB efficiently by opening tight junctions and inhibiting the efflux system of BBB. The targeted distribution of GO-PEG-BO in the brain was observed by an in vivo biodistribution study. Moreover, GO-PEG-BO exhibited a neuroprotective effect, which is beneficial to the treatment of depression. Ginsenoside Rg1 (GRg1), which can relieve depressive symptoms but difficult to cross BBB, was loaded to GO-PEG-BO for the therapy of depression. In depressive rats, GRg1/GO-PEG-BO improved stress-induced anhedonia, despair and anxiety, and comprehensively relieved the depressive symptoms. In conclusion, GO-PEG-BO could serve as a promising nanocarrier for brain-targeted drug delivery, and provide a new strategy for the therapy of depression.

Brain Targeted Drug Delivery System: A Review

Brain is the most sophisticated and important organ of our body. Together with spinal cord it control all actions, all functions voluntary or involuntary and plays a vital role in managing various organ systems of our body. It has its own protective barriers that protects the brain from various pathogens and toxins that may cause the harm. These barriers are namely Blood-Brain barrier and Blood-Cerebrospinal Fluid Barrier. The highly lipophilic nature of these barriers helps them in protecting the brain, allowing the passage of only highly lipophilic drugs to the brain through blood. However when there is an infection or injury in brain, the same barriers pose a hindrance in the delivery of drugs to the brain for treatment. Usually, drugs are usually hydrophilic in nature and since barriers of brain are lipophilic in nature, the finds it hard to cross these barriers and reach the brain. In order to overcome the problem in drug delivery to the brain as a target organ various drug delivery techniques were developed. Invasive and non-invasive approaches are two main approaches that are used to deliver drug to brain. In invasive approach the permeability of BBB is decreased or the drug is directly administered, whereas in non-invasive approach the drug molecule is altered to enhance its lipophilicity allowing its passage to the brain. This review aims to describe the various brain targeted drug delivery system..

Small extracellular vesicles: a novel drug delivery system for neurodegenerative disorders.

Neurodegenerative diseases (NDs) have a slow onset and are usually detected late during disease. NDs are often difficult to cure due to the presence of the blood-brain barrier (BBB), which makes it difficult to find effective treatments and drugs, causing great stress and financial burden to families and society. Currently, small extracellular vesicles (sEVs) are the most promising drug delivery systems (DDSs) for targeted delivery of molecules to specific sites in the brain as a therapeutic vehicle due to their low toxicity, low immunogenicity, high stability, high delivery efficiency, high biocompatibility and trans-BBB functionality. Here, we review the therapeutic application of sEVs in several NDs, including Alzheimer's disease, Parkinson's disease, and Huntington's disease, discuss the current barriers associated with sEVs and brain-targeted DDS, and suggest future research directions.

Recent Developments In Brain-Targeted Drug Delivery Systems via Intranasal Route

Diseases of the human nervous system such as neurological infections, Parkinson's, Alzheimer's, and other neurodegenerative diseases are severe pathological diseases and become a public health problem. Neurological disease in its treatment requires a drug distribution mechanism to reach the brain in sufficient quantities so that therapeutic effectiveness is achieved. This is very difficult to achieve with conventional treatment methods such as oral and injection because there are several obstacles in the process of drug distribution, one of which is an obstacle in the form of a Blood Brain Barrier (BBB). Along with current therapeutic developments, drug delivery modifications in the pharmaceutical field are increasingly being developed for the treatment of central nervous system (CNS) diseases. The intranasal drug delivery system to the brain via the nose is very interesting because this route can deliver drugs directly to the brain via the BBB. The intranasal route is preferred in brain targeting. This is due to the ability of the intranasal route to directly deliver drugs through the neural pathways, namely the olfactory nerve and the trigeminal nerve. By distributing the drug via the intranasal route, the drug will pass through the BBB and not undergo metabolism in the liver (first-pass metabolism), where this condition is a barrier that significantly inhibits the peripheral transport of drugs to the brain. There are several things that influence intranasal drug delivery, including parameters that affect intranasal drug administration, drug administration pathways, and mechanisms from the nose to the brain. An in vitro system that can be used to determine the permeability of drugs by means of nano and microparticles through olfactory mucosa cells. Positive results from in vitro experiments on rat test animals indicate that intranasal drug distribution guarantees the effectiveness of nanoparticle formulations in drug therapy. Seeing the big influence on the effectiveness of treatment methods in neurological diseases that must pass through the barrier in the form of the BBB, it is necessary to have further studies related to developing drug delivery via the intranasal route.

Development and Evaluation of Brain-targeted Drug and Gene Delivery System

New drug modalities such as nucleic acid, gene, cells, and nanoparticles are expected for treating refractory diseases. However, these drugs have larger size and low cell membrane permeability; therefore, drug delivery systems (DDS) are essential for delivery to the intended site at the organ and cellular level. In case of the brain, drug migration to the brain from blood circulation is extremely limited by the blood-brain barrier (BBB). Therefore, brain-targeted DDS technologies with the ability to overcome the BBB are being intensively developed. Ultrasound-mediated BBB opening can transiently permeabilize the BBB via cavitation and oscillation and is expected to transfer drugs into the brain. Besides several fundamental studies, clinical studies on BBB opening have also been undertaken, proving its efficacy and safety. Our group has developed an ultrasound-mediated DDS to the brain for low-molecular weight drugs as well as plasmid DNA and mRNA intended for gene therapy. We also evaluated the distribution of gene expression to obtain essential information for applying gene therapy. Here, I provide general information on DDS to the brain, and describe our research progress in brain-targeted delivery of plasmid DNA and mRNA using BBB opening.

Combined Biomimetic MOF-RVG15 Nanoformulation Efficient Over BBB for Effective Anti-Glioblastoma in Mice Model.

The blood-brain barrier (BBB) is a key obstacle to the delivery of drugs into the brain. Therefore, it is essential to develop an advanced drug delivery nanoplatform to solve this problem. We previously screened a small rabies virus glycoprotein 15 (RVG15) peptide with 15 amino acids and observed that most of the RVG15-modified nanoparticles entered the brain within 1 h of administration. The high BBB penetrability gives RVG15 great potential for brain-targeted drug delivery systems. Moreover, a multifunctional integrated nanoplatform with a high drug-loading capacity, tunable functionality, and controlled drug release is crucial for tumor treatment. Zeolitic imidazolate framework (ZIF-8) is a promising nanodrug delivery system. Inspired by the biomimetic concept, we designed RVG15-coated biomimetic ZIF-8 nanoparticles (RVG15-PEG@DTX@ZIF-8) for docetaxel (DTX) delivery to achieve efficient glioblastoma elimination in mice. This bionic nanotherapeutic system was prepared by one-pot encapsulation, followed by coating with RVG15-PEG conjugates. The size, morphology, stability, drug-loading capacity, and release of RVG15-PEG@DTX@ZIF-8 were thoroughly investigated. Additionally, we performed in vitro evaluation, cell uptake capacity, BBB penetration, and anti-migratory ability. We also conducted an in vivo evaluation of the biodistribution and anti-glioma efficacy of this bionic nanotherapeutic system in a mouse mode. In vitro studies showed that, this bionic nanotherapeutic system exhibited excellent targeting efficiency and safety in HBMECs and C6 cells and high efficiency in crossing the BBB. Furthermore, the nanoparticles cause rapid DTX accumulation in the brain, allowing deeper penetration into glioma tumors. In vivo antitumor assay results indicated that RVG15-PEG@DTX@ZIF-8 significantly inhibited glioma growth and metastasis, thereby improving the survival of tumor-bearing mice. Our study demonstrates that our bionic nanotherapeutic system using RVG15 peptides is a promising and powerful tool for crossing the BBB and treating glioblastoma.

Brain-Targeted Drug Delivery System: A Novel Approach

A targeted drug delivery system is based on a technique that continuously administers a predetermined dosage of a therapeutic agent to a sick location of the body. The targeted drug delivery goal is to raise the relative amount of the treatment in the target tissues while lowering it in the non-target tissues. This technique's intrinsic benefit has been reduced drug dose and adverse effects. Drug targeting in the brain is one of the most challenging issues in pharmaceutical research because the blood-brain barrier acts as an impermeable barrier for systemically delivered therapeutics and the brain extracellular matrix contributes to the poor distribution of locally delivered drugs. In the treatment of various Central nervous system (CNS) diseases, general approaches that can improve drug delivery to the brain are of great interest. Drugs are less harmful and more effective when they are administered close to where they would be most effective. Extreme research studies have recently concentrated on the development of fresh strategies for more successfully delivering medications to the brain in response to the shortcomings of the traditional delivery mechanism. This study thoroughly explains the obstacles involved in brain-targeted drug delivery, the process of drug transfer through Blood Brain Barrier, different techniques for brain-targeted drug delivery, and some recent breakthroughs in brain-targeted drug delivery.
 Keywords: Blood-brain barrier, Brain-targeted, Cerebrospinal fluid, Nanoparticles, Liposomes, Convection-enhanced drug delivery.

"Guide" of muscone modification enhanced brain-targeting efficacy and anti-glioma effect of lactoferrin modified DTX liposomes.

Glioma is one of the most aggressive malignant diseases for human health. It is difficult to resect completely due to their invasiveness. The targeted delivery, as a noninvasive approach, is a major strategy for the development of treatments for brain tumors. Lactoferrin (Lf) receptors are over-expressed in both brain endothelial cells and glioma cells. Macromolecular Lf modified nanoparticles have been shown to enhance the brain targeting. Muscone is a "guide" drug that have been demonstrated to promote liposomes into the brain by modification. To further enhance the brain-targeting efficacy of Lf modified carriers, we designed that Lf and muscone dual-modified liposomes cross blood-brain barrier (BBB) and target to brain for enhanced docetaxel (DTX) brain delivery. The results showed that we successfully prepared Lf and muscone dual-modified liposomes (Lf-LP-Mu-DTX), the number of Lf molecules connected to the surface of per liposome was 28. Lf-LP-Mu-DTX increased uptake in both U87-MG cells and hCMEC/D3 cells, enhanced penetration of U87-MG tumor spheroid and in vitro BBB model, had better in vitro and in vivo anti-tumor effects. In conclusion, "guide" of muscone modification enhanced brain-targeting efficacy of Lf modified liposomes, Lf and muscone dual-modified docetaxel loaded liposomes present a potential brain-targeting drug delivery system for use in the future treatment of gliomas.

Recent progresses in exosome-based systems for targeted drug delivery to the brain.

Despite the multiple ongoing and novel initiatives for developing brain-targeted drug delivery systems, insurmountable obstacles remain. A perfect drug delivery device that can bypass the brain-blood barrier and boost therapeutic efficacy is urgently needed for clinical applications. Exosomes hold unrivaled benefits as a drug delivery vehicle for treating brain diseases due to their endogenous and innate attributes. Unique properties, such as the ability to penetrate physical barriers, biocompatibility, innate targeting features, ability to leverage natural intracellular trafficking pathways, favored tumor homing, and stability, make exosomes suitable for brain-targeted drug delivery. Herein, we provide an overview of recent exosome-based drug delivery nanoplatforms and discuss how these inherent vesicles can be used to deliver therapeutic agents to the brain to cure neurodegenerative diseases, brain tumors, and other brain disorders. Moreover, we review the current roadblocks associated with exosomes and other brain-targeted drug delivery systems and discuss future directions for achieving successful therapy outcomes.