Search Results (323)

This narrative review explores the integration of theranostics and artificial intelligence (AI) in neuro-oncology, addressing the urgent need for improved diagnostic and treatment strategies for brain tumors, including gliomas, meningiomas, and pediatric central nervous system neoplasms. A comprehensive literature search was conducted through PubMed, Scopus, and Embase for articles published between January 2020 and May 2025, focusing on recent clinical and preclinical advancements in personalized neuro-oncology. The review synthesizes evidence on novel theranostic agents—such as Lu-177-based radiopharmaceuticals, CXCR4-targeted PET tracers, and multifunctional nanoparticles—and highlights the role of AI in enhancing tumor detection, segmentation, and treatment planning through advanced imaging analysis, radiogenomics, and predictive modeling. Key findings include the emergence of nanotheranostics for targeted drug delivery and real-time monitoring, the application of AI-driven algorithms for improved image interpretation and therapy guidance, and the identification of current limitations such as data standardization, regulatory challenges, and limited multicenter validation. The review concludes that the convergence of AI and theranostic technologies holds significant promise for advancing precision medicine in neuro-oncology, but emphasizes the need for collaborative, multidisciplinary research to overcome existing barriers and enable widespread clinical adoption. Full article

Advances in molecular diagnostics have enabled precision medicine approaches in pediatric neuro-oncology, with small-molecule drugs emerging as promising therapeutic candidates targeting specific genetic and epigenetic alterations in central nervous system (CNS) tumors. This review provides a focused overview of several small-molecule agents under investigation or in early clinical use, including ONC201, tazemetostat, vorasidenib, CDK inhibitors, selinexor, and aurora kinase A inhibitors, among others. Highlighted are their mechanisms of action, pharmacokinetic properties, early efficacy data, and tolerability in pediatric populations. Despite encouraging preclinical and early-phase results, most agents face limitations due to study heterogeneity, lack of large-scale pediatric randomized trials, and challenges in drug delivery to the CNS. The review underscores the critical need for robust prospective clinical trials for the integration of these therapies into pediatric neuro-oncology care. Full article

Donepezil (DPZ) is an Alzheimer’s disease (AD) drug that promotes cholinergic neurotransmission and exhibits excellent acetylcholinesterase (AChE) selectivity. The current oral formulations of DPZ demonstrate decreased bioavailability, attributed to limited drug permeability across the blood–brain barrier (BBB). In order to overcome these limitations, various dosage forms aimed at delivering DPZ have been explored. This discussion will focus on the nose-to-brain (N2B) delivery system, which represents the most promising approach for brain drug delivery. Intranasal (IN) drug delivery is a suitable system for directly delivering drugs to the brain, as it bypasses the BBB and avoids the first-pass effect, thereby targeting the central nervous system (CNS). Currently developed formulations include lipid-based, solid particle-based, solution-based, gel-based, and film-based types, and a systematic review of the N2B research related to these formulations has been conducted. According to the in vivo results, the brain drug concentration 15 min after IN administration was more than twice as high those from other routes of administration, and the direct delivery ratio of the N2B system improved to 80.32%. The research findings collectively suggest low toxicity and high therapeutic efficacy for AD. This review examines drug formulations and delivery methods optimized for the N2B delivery of DPZ, focusing on technologies that enhance mucosal residence time and bioavailability while discussing recent advancements in the field. Full article

Microneedle arrays (MNAs) are becoming increasingly popular due to their ease of use and effectiveness in drug delivery and diagnostic applications. Improvements in three-dimensional (3D) printing techniques have made it possible to fabricate MNAs with high precision, intricate designs, and customizable properties, expanding their potential in medical applications. While most studies have focused on transdermal applications, non-transdermal uses remain relatively underexplored. This review summarizes recent developments in 3D-printed MNAs intended for non-transdermal drug delivery and diagnostic purposes. It includes a literature review of studies published in the past ten years, organized by the target delivery site—such as the brain and central nervous system (CNS), oral cavity, eyes, gastrointestinal (GI) tract, and cardiovascular and reproductive systems, among other emerging areas. The findings show that 3D-printed MNAs are more adaptable than skin-based delivery, opening up exciting new possibilities for use in a variety of organs and systems. To guarantee the effective incorporation of polymeric non-transdermal MNAs into clinical practice, additional research is necessary to address current issues with materials, manufacturing processes, and regulatory approval. Full article

Brain metastases (BM), which most commonly originate from lung, breast, or skin cancers, remain a major clinical challenge, with standard treatments such as stereotactic radiosurgery (SRS), surgical resection, and whole-brain radiation therapy (WBRT). The prognosis for patients with BM remains poor, with a median overall survival (OS) of just 10–16 months. Although recent advances in systemic therapies, including small molecule inhibitors, monoclonal antibodies, chemotherapeutics, and gene therapies, have demonstrated success in other malignancies, their effectiveness in central nervous system (CNS) cancers is significantly limited by poor blood–brain barrier (BBB) permeability and subtherapeutic drug concentrations in the brain. Nanoparticle-based drug delivery systems have emerged as a promising strategy to overcome these limitations by enhancing CNS drug penetration and selectively targeting metastatic brain tumor cells while minimizing off-target effects. This review summarizes recent preclinical and clinical developments in nanoparticle-based therapies for BM. It is evident from these studies that NPs can carry with them a range of therapeutics, including chemotherapy, immunotherapy, small molecule inhibitors, gene therapies, radiosensitizers, and modulators of tumor microenvironment to the BM. Moreover, preclinical studies have shown encouraging efficacy in murine models, highlighting the potential of these platforms to improve therapeutic outcomes. However, clinical translation remains limited, with few ongoing trials. To close this translational gap, future work must address clinical challenges such as trial design, regulatory hurdles, and variability in BBB permeability while developing personalized nanoparticle-based therapies tailored to individual tumor characteristics. Full article

Central nervous system diseases are highly complex in terms of etiology and pathogenesis, making their treatment and interventions for them a major focus and challenge in neuroscience research. Anthocyanins, natural water-soluble pigments widely present in plants, belong to the class of flavonoid compounds. As natural antioxidants, anthocyanins have attracted extensive attention due to their significant functions in scavenging free radicals, antioxidation, anti-inflammation, and anti-apoptosis. The application of anthocyanins in the field of central nervous system injury, particularly in neurodegenerative diseases, neurotoxicity induced by chemical drugs, stress-related nerve damage, and cerebrovascular diseases, has achieved remarkable research outcomes. However, anthocyanins often exhibit low chemical stability, a short half-life, and relatively low bioavailability, which limit their clinical application. Recent studies have found that the stability and bioavailability of anthocyanins can be significantly improved through nanoencapsulation, acylation, and copigmentation, as well as the preparation of nanogels, nanoemulsions, and liposomes. These advancements offer the potential for the development of anthocyanins as a new type of neuroprotective agent. Future research will focus on the innovative design of nano-delivery systems and structural modification based on artificial intelligence. Such research is expected to break through the bottleneck of anthocyanin application and enable it to become a core component of next-generation intelligent neuroprotective agents. Full article

Being one of the most aggressive primary brain tumors, glioblastoma multiforme (GBM) is known from the median survivals of just 15 months following diagnosis. Conventional treatments, including surgical resection, radiotherapy, and chemotherapy, have limited efficiency due to the invasive nature of glioma cells and the presence of a blood–brain barrier. Therefore, adjuvant therapy in the form of a localized delivery of chemotherapeutic agents is indispensable to increase the chances of patients. Among a variety of advanced drug carriers, collagen has recently emerged as an excellent choice for regional chemotherapy, mainly due to its biocompatibility, biodegradability, weak antigenicity, biomimetics, and well-known safety profile, as well as its native presence in the extracellular matrix of the central nervous system. The aim of this paper is to highlight the most recent studies describing the application of collagen as a drug carrier able to provide an extended delivery of chemotherapeutic agents directly to the GBM site, and to provide exciting opportunities for its future applications. Full article

Extracellular vesicles (EVs) are bilayer lipid membrane particles that are released by every cell type. These secretions are further classified as exosomes, ectosomes, and microvesicles. They contain biomolecules (RNAs, proteins, metabolites, and lipids) with the ability to modulate various biological processes and have been shown to play a role in intercellular communication and cellular rejuvenation. Various studies suggest exosomes and/or microvesicles as a potential platform for drug delivery. EVs may deliver lipids and nucleotides directly to an injury site in an axon, promoting growth cone stabilization and membrane expansion as well as repair, thus positively modulating adult axon regeneration. In this review, we will provide a perspective on the metabolite composition of EVs in adult axonal regeneration relevant to the central nervous system (CNS), specifically that pertaining to the optic nerve. We will present an overview of the methods for isolation, enrichment, omics data analysis and quantification of extracellular vesicles with the goal of providing direction for future studies relevant to axon regeneration. We will also include current resources for multi-omics data integration relevant to extracellular vesicles from diverse cell types. Full article

Nose-to-brain drug delivery is an innovative approach that leverages the unique anatomical pathways connecting the nasal cavity to the brain, including the olfactory and trigeminal nerve routes. This method bypasses the blood–brain barrier, enabling direct and efficient transport of therapeutic agents to the central nervous system. It offers significant advantages, such as rapid drug action, reduced systemic side effects, and improved patient compliance through non-invasive administration. This entry summarizes factors affecting the nose-to-brain delivery of drugs and the recent development of nanoparticle-based nose-to-brain delivery. Full article

Cardiac glycosides (CGs), a class of plant- and animal-derived compounds historically used to treat heart failure, have garnered renewed interest for their diverse pharmacological properties beyond Na⁺/K⁺-ATPase (NKA) inhibition. Recent studies reveal that CGs modulate key signaling pathways—such as NF-κB, PI3K/Akt, JAK/STAT, and MAPK—affecting processes central to cancer, viral infections, immune regulation, and neurodegeneration. In cancer, CGs induce multiple forms of regulated cell death, including apoptosis, ferroptosis, pyroptosis, and immunogenic cell death, while also inhibiting angiogenesis, epithelial–mesenchymal transition, and cell cycle progression. They demonstrate broad-spectrum antiviral activity by disrupting viral entry, replication, and mRNA processing in viruses such as HSV, HIV, influenza, and SARS-CoV-2. Immunologically, CGs regulate Th17 differentiation via RORγ signaling, although both inhibitory and agonistic effects have been reported. In the nervous system, CGs modulate neuroinflammation, support synaptic plasticity, and improve cognitive function in models of Alzheimer’s disease, epilepsy, and multiple sclerosis. Despite their therapeutic potential, clinical translation is hindered by narrow therapeutic indices and systemic toxicity. Advances in drug design and nanocarrier-based delivery are critical to unlocking CGs’ full potential as multi-target agents for complex diseases. This review synthesizes the current knowledge on the emerging roles of CGs and highlights strategies for their safe and effective repurposing. Full article

Background: The blood–brain barrier (BBB) plays a critical role in protecting the central nervous system (CNS) but also limits drug delivery. Insufficient knowledge of how the CNS promotes the onset and maintenance of peripheral neuropathic pain limits therapeutic methods for the treatment of persistent neuropathic pain. Thus, this study aimed to evaluate the ability of a novel combination of Palmitoylethanolamide (PEA) and Equisetum arvense L. (Equisetum A.L.) to cross the BBB and modulate nociceptive pathways. Methods: Using a humanised in vitro BBB tri-culture model, the permeability, cytotoxicity, and integrity of the barrier were assessed after exposure to two different PEA forms, PEA ultramicronized (PEA-um) and PEA80mesh, Equisetum A.L., and a combination of the last two samples. The samples exhibited no cytotoxicity, maintained tight junction integrity, and efficiently crossed the blood–brain barrier (BBB), with the combination displaying the highest permeability. The eluate from the BBB model was then used to stimulate the co-culture of CCF-STTG1 astrocytes and SH-SY5Y neurons pre-treated with H₂O₂ 200 µM. Results: Treatment with the combination significantly increased cell viability (1.8-fold, p < 0.05), reduced oxidative stress (2.5-fold, p < 0.05), and decreased pro-inflammatory cytokines (TNFα, IL-1β) compared to single agents. Mechanistic analysis revealed modulation of key targets involved in pain pathways, including decreased FAAH and NAAA activity, increased levels of endocannabinoids (AEA and 2-AG), upregulation of CB2 receptor expression, enhanced PPARα activity, and reduced phosphorylation of PKA and TRPV1. Conclusions: These findings suggest that the combination of PEA and Equisetum A.L. effectively crosses the BBB and exerts combined anti-inflammatory and analgesic effects at the CNS level, suggesting a possible role in modulating neuroinflammatory and nociception responses. Full article

As population aging becomes an increasingly critical global issue, the incidence of central nervous system (CNS) diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and stroke, has risen sharply. However, the blood–brain barrier (BBB) presents a significant obstacle to the effective treatment of these CNS disorders, limiting the ability of therapeutic agents to reach the brain. In this context, intranasal drug delivery, which bypasses the BBB, has attracted considerable attention in recent years. By utilizing pathways such as the olfactory and trigeminal nerves, intranasal drug delivery facilitates the rapid transport of drugs to the brain, thereby enhancing both the bioavailability and targeting efficiency of the drugs. This review provides an overview of the molecular mechanisms underlying intranasal drug delivery, its advancements in the treatment of CNS diseases, strategies to improve delivery efficiency, and a discussion of the challenges and potential future directions in this field. The aim of this paper is to offer valuable insights and guidance for researchers and clinicians working in the area of CNS disease treatment. Full article

Background/Objectives: Non-invasive central nervous system (CNS) therapies are limited by complex mechanisms and the blood–brain barrier, but nasal delivery offers a promising alternative. The study planned to develop a non-invasive in situ intranasal mucoadhesive thermosensitive gel to deliver CNS-active risperidone via nose-to-brain targeting. Risperidone, a second-generation antipsychotic, has shown efficacy in managing both psychotic and mood-related symptoms. The mucoadhesive gel formulations help to prolong the residence time at the nasal absorption site, thereby facilitating the uptake of the drug. Methods: The poloxamer 407 (18.0% w/v), HPMC K100M and K15M (0.3–0.5% w/v), and benzalkonium chloride (0.1% v/v) were used as thermosensitive polymers, a mucoadhesive agent, and a preservative, respectively, for the development of in situ thermosensitive gel. The developed formulations were evaluated for various parameters. Results: The pH, gelation temperature, gelation time, and drug content were found to be 6.20 ± 0.026–6.37 ± 0.015, 34.25 ± 1.10–37.50 ± 1.05 °C, 1.65 ± 0.30–2.50 ± 0.55 min, and 95.58 ± 2.37–98.03 ± 1.68%, respectively. Furthermore, the optimized F3 formulation showed satisfactory gelling capacity (9.52 ± 0.513 h) and an acceptable mucoadhesive strength (1110.65 ± 6.87 dyne/cm²). Diffusion of the drug through the egg membrane depended on the formulation’s viscosity, and the F3 formulation explained the first-order release kinetics, indicating concentration-dependent drug diffusion with n < 0.45 (0.398) value, indicating the Fickian-diffusion (diffusional case I). The pharmacokinetic study was performed with male Wistar albino rats, and the F3 in situ thermosensitive risperidone gel confirmed significantly (p < 0.05) ~5.4 times higher brain AUC_0–∞ when administered intranasally compared to the oral solution. Conclusions: Based on physicochemical, in vitro, and in vivo parameters, it can be concluded that in situ thermosensitive gel is suitable for administration of risperidone through the nasal route and can enhance patient compliance through ease of application and with less repeated administration. Full article

The intestine is an important segment of the gastrointestinal tract, which is involved in complex processes that maintain the body’s normal homeostasis. It hosts a vast, diverse, and dynamic microbial community called the gut microbiota, which develops from birth. It has been observed that the gut microbiota is involved in essential physiological processes, including the development of the central nervous system via the gut microbiota–brain axis. An alteration of the gut microbiota can lead to serious health problems, including defective neurodevelopment. Thus, this paper aims to highlight the most recent advances in studies that focus on the link between the gut microbiota and the evolution of neurodevelopmental diseases in children. Currently, studies show that the use of drugs that stimulate and restore the gut microbiota (e.g., probiotics and prebiotics) have the potential to alleviate some of the symptoms associated with conditions such as Autism Spectrum Disorder, Attention Deficit Hyperactivity Disorder, Tic Disorder, Tourette Syndrome, epilepsy, and Down Syndrome. In addition, due to the challenges associated with drug administration in children, as well as the widespread shortage of medications intended for pediatric use, researchers are working on the development of new delivery systems. Liposome-based systems or solid lipid nanoparticles have been safely used for drug delivery in various pediatric conditions, which may also indicate their potential for use in the administration of microbiota-modulating therapies. Full article

The blood–brain barrier (BBB) is a highly selective and natural protective membrane that restricts the entry of therapeutic agents into the central nervous system (CNS). This restrictive nature poses a major challenge for pharmacological treatment of a wide range of CNS disorders, including neurodegenerative disorders, brain tumors, and psychiatric conditions. Many chemical drugs and biopharmaceuticals are unable to cross the BBB, and conventional drug delivery methods often fail to achieve sufficient brain concentrations, leading to reduced therapeutic efficacy and increased risk of systemic toxicity. In recent years, targeted drug delivery strategies have emerged as promising approaches to overcome the BBB and enhance the delivery of therapeutic agents to the brain. Among these, receptor-mediated transcytosis (RMT) and transporter-mediated transcytosis (TMT) are two of the most extensively studied mechanisms for transporting drugs across brain endothelial cells into the brain parenchyma. Advances in materials science and nanotechnology have facilitated the development of multifunctional carriers with optimized properties, improving drug targeting, stability, and release profiles within the brain. This review summarizes the physiological structure of the BBB and highlights recent innovations in RMT- and TMT-mediated brain drug delivery systems, emphasizing their potential not only to overcome current challenges in CNS drug development, but also to pave the way for next-generation therapies that enable more precise, effective, and personalized treatment of brain-related diseases. Full article