Brain Drug Research Articles

Rizatriptan loaded Bilosomes for Nose to Brain Delivery: Fabrication, Statistical Optimization, and Biological Evaluation

Rizatriptan (RTP) is an anti-migraine drug and after oral administration, it exhibits low bioavailability (45%) due to high first-pass hepatic metabolism. Therefore, to resolve this issue, RTP-loaded bilosomes (BLSs) for brain delivery through the intranasal route were developed. RTP-BLSs were prepared by the thin-film hydration technique and optimized by the L9 Taguchi model. Bile salt (sodium glycocholate, mg), surfactant (Span 40, mg), and edge activator (Cremophor RH 40, mg) were selected as independent factors and their influence was observed on vesicle size (nm) and entrapment efficiency (%). Selected optimized RTP-BLSs (F5) have low vesicle size (204.70 ± 5.8 nm) and polydispersity index (0.260 ± 0.022), good entrapment efficiency (78.32 ± 3.1%), and high zeta potential (-27.6 ± 1.67 mV). The optimized RTP-BLSs exhibited a more sustained released profile (96.41 ± 4.48 % in 24 h) than RTP-Sol (98.65 ± 3.46 % RTP released in 4 h). The flux and apparent permeability coefficient for optimized RTP-BLSs were calculated and found to be 1.069 ± 0.026 μg.cm-2.h1 and 10.690×10-4 ± 0.262×10-4 cm.h-1) and comparatively (P<0.05) better than RTP-Sol (0.548 ± 0.148 μg.cm-2.h-1 and 5.481×10-4 ± 1.476 ×10-4 cm.h-1). The relative bioavailability of RTP formulated within the optimized RTP-BLSs administered intranasally was 2.94 ± 0.78-fold higher than the one obtained with RTP-Sol. The optimized RTP-BLSs showed 1.91 ± 0.15-fold higher absolute bioavailability as compared to intravenous administration RTP-BLSs. The optimized RTP-BLSs showed 64.18 ± 2.34% nose-to-brain drug transport, while RTP-Sol exhibited 20.72 ± 1.46% after intranasal administration. The optimized RTP-BLSs showed a significantly higher brain drug targeting efficiency (279.16 ± 6.37%) as compared to RTP-Sol (126.15 ± 4.79%) given intranasally. From our findings, it can be concluded that the developed BLSs are novel alternative RTP carriers for direct nose-to-brain delivery for the improvement of brain drug targeting.

Revolutionizing Brain Drug Delivery: Buccal Transferosomes on the Verge of a Breakthrough.

The buccal cavity, also known as the oral cavity, is a complex anatomical structure that plays a crucial role in various physiological processes. It serves as a gateway to the digestive system and facilitates the initial stages of food digestion and absorption. However, its significance extends beyond mere digestion as it presents a promising route for drug delivery, particularly to the brain. Transferosomes are lipid-based vesicles that have gained significant attention in the field of drug delivery due to their unique structure and properties. These vesicles are composed of phospholipids that form bilayer structures capable of encapsulating both hydrophilic and lipophilic drugs. Strategies for the development of buccal transferosomes for brain delivery have emerged as promising avenues for pharmaceutical research. This review aims to explore the various approaches and challenges associated with harnessing the potential of buccal transferosomes as a means of enhancing drug delivery to the brain. By understanding the structure and function of both buccal tissue and transferosomes, researchers can develop effective formulation methods and characterization techniques to optimize drug delivery. Furthermore, strategic approaches and success stories in buccal transferosome development are highlighted, showcasing inspiring examples that demonstrate their potential to revolutionize brain delivery.

Brain Drug Delivery- An Updated Review Article for Mechanism and Recent Technologies

Brain Drug Delivery- An Updated Review Article for Mechanism and Recent Technologies

EXTH-57. EXPLORING NOVEL ROUTES FOR NON-INVASIVE DRUG ADMINISTRATION: INTRADERMAL DELIVERY FOR THE TREATMENT OF BRAIN TUMORS

Abstract Effective non-invasive drug delivery to brain tumors remains challenging, despite extensive exploration of these methods, due to the blood-brain barrier (BBB). Intranasal drug delivery has emerged as a promising alternative approach, as it circumvents limitations on tumor access imposed by the BBB when administering therapeutics systemically and limits the occurrence of systemic toxic responses to treatment. The intranasal route of administration allows therapeutic access to brain tumors through pathways involving the olfactory and trigeminal nerves (TNs) that connect the nasal passage to the brain. However, effective nose-to-brain delivery is impeded by rapid mucosal drug clearance in the nasal cavity, drug aspiration, and ingestion. Since the TN arises from the brainstem and its branches innervate the facial skin, in addition to muscles, meninges, and respiratory mucosa, we tested the hypothesis that facial intradermal administration targeting the V2 branch of the TN could be an alternative strategy to harness TN-mediated brain delivery to bypass the BBB. Here, we developed Spherical Nucleic Acids (SNAs) consisting of a 15nm spherical gold nanoparticle core functionalized with radially oriented fluorophore-tagged ssDNA as a model therapeutic. We observed the delivery of the SNAs to the brain starting 4 hours post intradermal injection, with the SNA accumulation in the tumor persisting over time. Using ex vivo fluorescent imaging, comprehensive immunofluorescence microscopy, and flow cytometry we confirmed the SNA accumulation in the brain, dura, TN, and cervical lymph nodes. In particular, we demonstrated that SNAs were enriched in the neuronal cell bodies of the trigeminal ganglia and within the epineurium and perineurium of the TN. The SNAs were also enriched in CD45-positive immune cells. In conclusion, this study credentialed facial intradermal administration of SNAs as a promising non-invasive method for brain drug delivery to target intracranial tumors.

Brain drug delivery from the nasal olfactory region is enhanced using lauroylcholine chloride: An estimation using in vivo PET imaging

IntroductionIntranasal (IN) administration, often referred to as nose-to-brain (N2B) drug delivery, is an attractive approach for delivering drugs to the central nervous system. However, the efficacy of this method is limited because of the small size of the nasal olfactory region, which limits the drug dosage. Using permeation enhancers could improve drug delivery from this region to the brain, though their effects are not fully understood. We therefore investigated the effects of co-administration of permeation enhancers on N2B drug delivery of a model drug domperidone, a peripherally acting dopamine D2 receptor (D2R) blocker. MethodsWe conducted in vitro permeability assays to evaluate the effects of sodium lauryl sulfate (SLS), a classical permeation enhancer, and lauroylcholine chloride (LCC) on domperidone permeation in human nasal mucosa-derived cells. We also used the D2R ligand [11C]raclopride to assess the in vivo effects of LCC on domperidone delivery in the rat brain using a positron emission tomography (PET) competition paradigm. In comparative PET experiments, we tested the effects of intravenously administered domperidone without LCC co-administration. ResultsLCC effectively improved nasal mucosal permeation of domperidone in vitro compared to SLS. In rat IN administration experiments, striatal [11C]raclopride uptake was significantly decreased by the addition of LCC to domperidone. On the other hand, intravenously administered domperidone with or without intranasally administered LCC did not decrease [11C]raclopride brain uptake, suggesting a lesser influence of peripheral domperidone on [11C]raclopride brain uptake. PET studies showed that striatal D2R occupancy of domperidone was increased 2.4-fold by co-administration of LCC. ConclusionLCC effectively enhances the domperidone delivery from the rat olfactory region to the brain, probably not via a circulating blood. The combination of permeation enhancers and olfactory region-selective drug administration could be effective for N2B drug delivery.

Lyotropic Liquid Crystalline Based Nasal Spray for Improved Parkinson's Treatment: Enhanced Superior Nasal Tract Deposition and Antioxidation Strategy

AbstractThe blood–brain barrier is one of the serious challenges in the treatment of Parkinson's disease (PD), which severely hinders the drug's brain bioavailability. In this study, a lyotropic liquid crystalline (LLC) based in situ gel nasal spray loaded with the first‐line drug Levodopa (LDA) for PD is developed to resolve this issue based on a nose‐to‐brain drug delivery approach. Specifically, the two key stages of LLC‐based in situ gel nasal spray, droplet deposition, and drug retention are tailored. By adjusting LLC's precursor solution's viscosity, the droplet deposition on the superior nasal tract can be increased by 18 times. Through nasal mucus‐triggered sol–gel transition, the LDA nasal cavity retention is prolonged by three times. The epigallocatechin gallate is incorporated into the LLC‐based in situ gel nasal spray to inhibit the autoxidation of LDA and alleviate the oxidative stress response in PD. The results show that the LLC‐based in situ gel nasal spray has a 26‐fold higher brain bioavailability of LDA compared to oral administration. The PD rats show a significant improvement in behavioral and cognitive disorders after administration. The LLC‐based in situ gel nasal spray is proved to work by reducing oxidative damage. This study is anticipated to offer a promising strategy for the clinical application of LDA.

Systematic Approach in the Development of Chitosan Functionalized Iloperidone Nanoemulsions for Transnasal Delivery, In Vitro and In Vivo Studies.

Iloperidone, a second-generation USFDA approved antipsychotic and BCS class II drug shows poor oral bioavailability of 28%. The present research deals with optimization of transnasal nanoemulsions of Iloperidone using Design Expert (Version 11) and further surface functionalization with chitosan for potentiating nose to brain delivery. Chitosan functionalized transnasal Iloperidone nanoemulsions were developed using oleic acid, charge inducer, Tween 80, TranscutolHP and chitosan using ultrasonication technique and evaluated. Droplet size, polydispersity index and zeta potential of Iloperidone nanoemulsions was found to be 173 ± 0.5nm, 0.413 ± 0.2 and - 22.5 ± 0.1mV while that of chitosan functionalized Iloperidone nanoemulsions was 146.4 ± 0.5nm, 0.291 ± 0.02 and + 23.6 ± 0.3mV respectively. Ninhydrin assay, TEM and FTIR studies confirmed surface functionalization of Iloperidone nanoemulsion droplets with chitosan. In vitro release of Iloperidone from nanoemulsions and chitosan functionalized nanoemulsions was 90.41 ± 2.1% and 72.02 ± 0.21% while ex vivo permeation of Iloperidone across goat nasal mucosa was 1270.58 ± 0.023μg/cm2 and 1096.13 ± 0.043μg/cm2 respectively at the end of 8h. Studies in RPMI 2650 nasal and Neuro2A brain cell line lines indicated safety of chitosan functionalized transnasal Iloperidone nanoemulsions. Studies in Wistar rats showed increased cataleptic effects, reduced cognitive impairment and anxiety-related behaviour with greater brain accumulation indicating promising potential of this approach in nose to brain drug delivery.

All Blood Brain Barrier Cell Types Demonstrate Capability to Influence Differential Tenofovir and Emtricitabine Metabolism and Transport in the Brain.

The blood brain barrier (BBB) represents a significant obstacle in brain drug penetration that challenges efforts in the treatment of neurological disorders. Therapeutically targeting the brain requires interactions with each BBB cell type, including endothelial cells, pericytes, and astrocytes. Yet, the relative contribution of these BBB cell types to the mechanisms that facilitate brain drug disposition is not well characterized. Here, we use first-line antiretroviral therapies, tenofovir (TFV) and emtricitabine (FTC), as models to investigate the mechanisms of drug transport and metabolism at the BBB that may influence access of the drug to the brain. We evaluated regional and cell-type-specific drug metabolism and transport mechanisms using rhesus macaques and in vitro treatment of primary human cells. We report heterogeneous distribution of TFV, FTC, and their active metabolites, which cerebrospinal fluid measures could not reflect. We found that all BBB cell types possessed functional drug-metabolizing enzymes and transporters that promoted TFV and FTC uptake and pharmacologic activation. Pericytes and astrocytes emerged as pharmacologically dynamic cells that rival hepatocytes and were uniquely susceptible to modulation by disease and treatment. Together, our findings demonstrate the importance of considering the BBB as a unique pharmacologic entity rather than viewing it as an extension of the liver, as each cell type possesses distinct drug metabolism and transport capacities that contribute to differential brain drug disposition. Further, our work highlights pharmacologically active pathways at the BBB that may regulate brain drug disposition and impact therapeutic efforts to alleviate neurologic disease.

Rhamnosomes: A new generation of flexible vesicles for a boosted targeted nose-to-brain delivery of selegiline in the treatment of Parkinson's disease

Extensive hepatic metabolism of Selegiline, a selective monoamine oxidase B inhibitor for newly diagnosed Parkinson's disease patients, causes limited brain bioavailability. To improve efficacy, a new generation of flexible lipidic vesicles, Rhamnosomes, comprising alternating lecithin and Rhamnolipid moieties, and decorated with lactoferrin to actively target Selegiline to the brain is proposed.Rhamnosomes were optimized using design of expert, where lipid amount, Soybean lecithin:Rhamnolipid ratio and sonication time were varied. Polyelectrolyte complexation was employed for Lactoferrin conjugation to Rhamnosomes. A pharmacokinetic study in rat plasma and brain was conducted. Optimized Rhamnosomes had a particle size of 107 nm, polydispersity index of 0.23, zeta potential of −41mV, entrapment efficiency of 78 %, relative deformability of 36sec and ex-vivo skin permeation reaching 60 % after 24 h. The plasma half life of Rhamnosomes was 3.24 times the market product and 2.63 times the intravenous solution, whereas, lactoferrin-conjugated Rhamnosomes exhibited 7 times higher absolute bioavailability than the market product and more than double its brain drug targeting efficiency. Prominent direct nose-to-brain transport values further proved the efficiency of intranasally delivered Selegiline-loaded Lactoferrin conjugated Rhamnosomes to actively target the brain in a non-invasive approach for the treatment of Parkinson's disease.

Knowledge, Attitudes, and Perceptions of Mental Disorders Among Young Adults: Addressing Stigma and the Need for Mental Health Care

This study explores the knowledge, attitudes, and perceptions of young adults towards mental disorders and mental health care needs. Using a quantitative research design, data was collected from 170 participants via a structured questionnaire administered online. Descriptive statistics were employed to analyze the data, revealing key insights into demographic characteristics and respondents' views on mental health. The findings indicate a strong consensus on the importance of mental health as a vital component of overall well-being, with moderate agreement on the causes of mental disorders, such as brain diseases, genetic inheritance, and drug abuse. However, misconceptions persist, particularly regarding supernatural causes and the stigma associated with mental illness. While young adults generally hold positive attitudes towards individuals with mental disorders, some stigmatizing beliefs still exist. The study also highlights a widespread recognition of the need for mental health care, with an overwhelming majority of respondents advocating for professional help and open discussions about mental health concerns. These findings underscore the necessity of addressing mental health stigma and promoting awareness and education among young adults to foster a more supportive and understanding environment for those affected by mental disorders.

Optimizing Brain Drug Delivery: The Role of Nanosuspension in Enhancing Therapeutic Efficacy and Bioavailability

Optimizing Brain Drug Delivery: The Role of Nanosuspension in Enhancing Therapeutic Efficacy and Bioavailability

Understanding drug craving: evidence from fMRI studies

Drug craving is a major crisis experienced by active or former drug abusers. The experience is characterised by an intense desire to abuse drugs for self-pleasure and satisfaction. This desire appears to be the main culprit behind the skyrocketing relapse rate. Neuroimaging has identified neural substrates associated with drug cravings. Here, we provide a mini-review of functional magnetic resonance imaging (fMRI) studies that have examined the brain regions associated with the common types of drug abuse — heroin, methamphetamine, and cocaine. Most studies use visual cues (that is drug-related images) to elicit brain responses in reward-related pathways. Studies have also focused on comparing brain activities between active drug abusers, drug-abstinent individuals, and healthy controls. Current evidence suggests that the dorsolateral prefrontal cortex (DLPFC) is associated with heroin craving, whereas the ventral striatum and medial prefrontal cortex (mPFC) underpin methamphetamine craving. Meanwhile, the hypothalamus is responsible for cocaine cravings. Compared to active drug abusers, drug-abstinent individuals demonstrated fewer brain activations when viewing drug-related images. The relationship between brain response and drug cravings is discussed in terms of brain functions and drug types. The findings offer valuable insights into the potential role of these brain areas in drug cravings and have important implications for drug addiction treatments.

A comparison of the antiepileptogenic efficacy of two rationally chosen multitargeted drug combinations in a rat model of posttraumatic epilepsy

Post-traumatic epilepsy (PTE) is a recurrent and often drug-refractory seizure disorder caused by traumatic brain injury (TBI). No single drug treatment prevents PTE, but preventive drug combinations that may prophylax against PTE have not been studied. Based on a systematic evaluation of rationally chosen drug combinations in the intrahippocampal kainate (IHK) mouse model of acquired epilepsy, we identified two multi-targeted drug cocktails that exert strong antiepileptogenic effects. The first, a combination of levetiracetam (LEV) and topiramate, only partially prevented spontaneous recurrent seizures in the model. We therefore added atorvastatin (ATV) to the therapeutic cocktail (TC) to increase efficacy, forming “TC-001”. The second cocktail – a combination of LEV, ATV, and ceftriaxone, termed “TC-002” – completely prevented epilepsy in the mouse IHK model. In the present proof-of-concept study, we tested whether the two drug cocktails prevent epilepsy in a rat PTE model in which recurrent electrographic seizures develop after severe rostral parasagittal fluid percussion injury (FPI). Following FPI, rats were either treated over 3–4 weeks with vehicle or drug cocktails, starting either 1 or 4–6 h after the injury. Using mouse doses of TC-001 and TC-002, no significant antiepileptogenic effect was obtained in the rat PTE model. However, when using allometric scaling of drug doses to consider the differences in body surface area between mice and rats, PTE was prevented by TC-002. Furthermore, the latter drug cocktail partially prevented the loss of perilesional cortical parvalbumin-positive GABAergic interneurons. Plasma and brain drug analysis showed that these effects of TC-002 occurred at clinically relevant levels of the individual TC-002 drug components. In silico analysis of drug-drug brain protein interactions by the STITCH database indicated that TC-002 impacts a larger functional network of epilepsy-relevant brain proteins than each drug alone, providing a potential network pharmacology explanation for the observed antiepileptogenic and neuroprotective effects observed with this combination.

A multichannel microfluidic device for revealing the neurotoxic effects of Bisphenol S on cerebral organoids under low-dose constant exposure

Bisphenol S is a widely used plasticizer in manufacturing daily supplies, while little was known about its adverse effect on human health, especially on fetal brain development. Due to the complexity and subtlety of the brain, it remains challenging to reveal the hazardous effects of environmental pollution on human fetal brain development. Taking advantage of stem cell application, cerebral organoids generated from stem cells are becoming powerful tools for understanding brain development and drug toxicity testing models. Here, we developed a microfluidic chip for cerebral organoid culturing to reveal the neurotoxicity of low-dose constant BPS exposure on cerebral organoids. The organoids in our microfluidic system could be continuously cultured for 34 days and expressed all the essential properties of the cerebral organoids. Exposure to BPS was initiated from day 20 for concessive two weeks. The neurotoxic effects were evaluated by immunofluorescence staining and proteomics, and verified by quantitative real-time PCR. Our results indicated BPS exposure would inhibit neuron differentiation, hinder the Wnt signaling pathway, and cause alteration of signaling molecule expressions in brain regionalization. Even exposure to a low dose of BPS constantly might cause neurotoxicity during fetal brain development. Altogether, the multichannel microfluidic chip offers a general platform technique to reveal the effects of different hazardous chemicals on cerebral organoids.

Exploiting the mechanical effects of ultrasound for noninvasive therapy.

Focused ultrasound is a platform technology capable of eliciting a wide range of biological responses with high spatial precision deep within the body. Although focused ultrasound is already in clinical use for focal thermal ablation of tissue, there has been a recent growth in development and translation of ultrasound-mediated nonthermal therapies. These approaches exploit the physical forces of ultrasound to produce a range of biological responses dependent on exposure conditions. This review discusses recent advances in four application areas that have seen particular growth and have immense clinical potential: brain drug delivery, neuromodulation, focal tissue destruction, and endogenous immune system activation. Owing to the maturation of transcranial ultrasound technology, the brain is a major target organ; however, clinical indications outside the brain are also discussed.

Development and validation of an LC-MS/MS method for simultaneous quantification of eight drugs in plasma and brain: Application in a pharmacokinetic study in mice

A selective and sensitive liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) method was developed and validated for simultaneous quantitation of a cassette of 8 drugs, including docetaxel, erlotinib, loperamide, riluzole, vemurafenib, verapamil, elacridar and tariquidar. Stable isotopically labeled compounds were available for use as internal standards for all compounds, except for tariquidar for which we used elacridar-d4. Sample pre-treatment involved liquid–liquid extraction using tert-butyl-methyl ether as this resulted in good recovery and low ion suppression. Chromatographic separation was achieved using a Zorbax Extend C18 analytical column and a linear gradient from 20 % to 95 % methanol in 0.1 % (v/v) formic acid in water. MS/MS detection using multiple reaction monitoring was done in positive ionization mode. We validated this assay for human and mouse plasma and mouse brain homogenates. The calibration curves were linear over a range 1–200 nM for each drug in the mix, except for tariquidar probably due to the lack of a stable isotope labeled analog. The intra-day and inter-day accuracies were within the 85–115 % range for all compounds at low, medium and high concentrations in the three different matrices. Similarly, the precision for all compounds at three different concentration levels ranged below 15 %, with the exception of tariquidar in mouse plasma and brain homogenate and riluzole in brain homogenate. Pilot studies have confirmed that the method is suitable for the analysis of mouse plasma samples and brain homogenates following cassette dosing of this mixture in mice.

In Vitro Drug Delivery through the Blood–Brain Barrier Using Cold Atmospheric Plasma

This study explores the potential of cold atmospheric plasma (CAP) to facilitate the delivery of large-molecule drugs to the brain. The blood–brain barrier (BBB) restricts the passage of most drugs, hindering treatment for neurological disorders. CAP generates reactive oxygen and nitrogen species (RONS) that may disrupt the BBB’s tight junctions, potentially increasing drug permeability. An in vitro BBB model and an immortalized cell line (bEND.3) were used in this experiment. Fluorescein isothiocyanate dextran (FD-4), a model drug, was added to the cells to determine drug permeability. Custom microplasma was used to produce reactive oxygen species (ROS). Trans-endothelial electrical resistance (TEER) measurements assessed the integrity of the BBB after the CAP treatment. A decrease in TEER was observed in the CAP-treated group compared to the controls, suggesting increased permeability. Additionally, fluorescence intensity measurements from the basal side of the trans-well plate indicated higher drug passage in the CAP-treated group. Moreover, the higher presence of ROS in the plasma-treated cells confirmed the potential of CAP in drug delivery. These findings suggest that CAP may be a promising approach for enhancing brain drug delivery.

Utilizing Multifaceted Approaches to Target Drug Delivery in the Brain: From Nanoparticles to Biological Therapies.

The blood-brain barrier (BBB) poses an important obstacle to treating neurological disorders because it limits the entry of therapeutic agents into the central nervous system (CNS). Surmounting this barrier is crucial for delivering drugs effectively and targeting precise areas of the brain affected by conditions like Parkinson's disease, Alzheimer's disease, and brain tumors. This review examines the diverse strategies employed to enhance brain targeting, including nanotechnology, viral vectors, and biological therapies. Nanoparticles, liposomes, and dendrimers offer promising approaches for encapsulating drugs and facilitating their transport across the BBB. Viral vectors, such as adeno-associated viruses, demonstrate high transfection efficiency for gene therapy applications in CNS diseases. Biological therapies, including stem cell transplantation and neuromodulation techniques, can potentially restore normal cellular function and treat genetic disorders. Challenges such as BBB permeability, safety concerns, and regulatory considerations are discussed, along with future perspectives on precision medicine, noninvasive delivery methods, and biomarker discovery. By addressing these challenges and embracing innovative approaches, the field of brain drug targeting aims to transfer the way that neurological illness is treated and improve patient outcomes.

Key Challenges, Influencing Factors, and Future Perspectives of Nanosuspensions in Enhancing Brain Drug Delivery.

Many brain diseases pose serious challenges to human life. Alzheimer's Disease (AD) and Parkinson's Disease (PD) are common neurodegenerative diseases that seriously threaten human health. Glioma is a common malignant tumor. However, drugs cannot cross physiological and pathological barriers and most therapeutic drugs cannot enter the brain because of the presence of the Blood-brain Barrier (BBB) and Bloodbrain Tumor Barrier (BBTB). How to enable drugs to penetrate the BBB to enter the brain, reduce systemic toxicity, and penetrate BBTB to exert therapeutic effects has become a challenge. Nanosuspension can successfully formulate drugs that are difficult to dissolve in water and oil by using surfactants as stabilizers, which is suitable for the brain target delivery of class II and IV drugs in the Biopharmaceutical Classification System (BCS). In nanosuspension drug delivery systems, the physical properties of nanostructures have a great impact on the accumulation of drugs at the target site, such as the brain. Optimizing the physical parameters of the nanosuspension can improve the efficiency of brain drug delivery and disease treatment. Therefore, the key challenges, influencing factors, and future perspectives of nanosuspension in enhancing brain drug delivery are summarized and reviewed here. This article aims to provide a better understanding of nanosuspension formulation technology used for brain delivery and strategies used to overcome various physiological barriers.

Metal-Organic Frameworks for Overcoming the Blood-Brain Barrier in the Treatment of Brain Diseases: A Review.

The blood-brain barrier (BBB) plays a vital role in safeguarding the central nervous system by selectively controlling the movement of substances between the bloodstream and the brain, presenting a substantial obstacle for the administration of therapeutic agents to the brain. Recent breakthroughs in nanoparticle-based delivery systems, particularly metal-organic frameworks (MOFs), provide promising solutions for addressing the BBB. MOFs have become valuable tools in delivering medications to the brain with their ability to efficiently load drugs, release them over time, and modify their surface properties. This review focuses on the recent advancements in molecular-based approaches for treating brain disorders, such as glioblastoma multiforme, stroke, Parkinson's disease, and Alzheimer's disease. This paper highlights the significant impact of MOFs in overcoming the shortcomings of conventional brain drug delivery techniques and provides valuable insights for future research in the field of neurotherapeutics.