Recent Advances in Intranasal Administration for Brain-Targeting Delivery: A Comprehensive Review of Lipid-Based Nanoparticles and Stimuli-Responsive Gel Formulations

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 1767 - 1807

Published: Feb. 1, 2024

Abstract: Addressing disorders related to the central nervous system (CNS) remains a complex challenge because of presence blood-brain barrier (BBB), which restricts entry external substances into brain tissue. Consequently, finding ways overcome limited therapeutic effect imposed by BBB has become goal in advancing delivery systems targeted brain. In this context, intranasal route emerged as promising solution for delivering treatments directly from nose through olfactory and trigeminal nerve pathways thus, bypassing BBB. The use lipid-based nanoparticles, including nano/microemulsions, liposomes, solid lipid nanostructured carriers, shown promise enhancing efficiency nose-to-brain delivery. These nanoparticles facilitate drug absorption nasal membrane. Additionally, situ gel (ISG) gained attention owing its ability extend retention time administered formulations within cavity. When combined with ISG creates synergistic effect, further overall effectiveness brain-targeted strategies. This comprehensive review provides thorough investigation administration. It delves strengths limitations specific considering anatomical complexities influential factors that play role during dosing. Furthermore, study introduces strategic approaches incorporating framework applications. Finally, recent information on approved products clinical trial status administration, along inclusion quality-by-design–related insights. Keywords: system, based nanoparticle, gel,

Language: Английский

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Blood–Brain Barrier-Targeting Nanoparticles: Biomaterial Properties and Biomedical Applications in Translational Neuroscience

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(5), P. 612 - 612

Published: May 10, 2024

Overcoming the blood–brain barrier (BBB) remains a significant hurdle in effective drug delivery to brain. While BBB serves as crucial protective barrier, it poses challenges delivering therapeutic agents their intended targets within brain parenchyma. To enhance for treatment of neurological diseases, several technologies circumvent have been developed last few years. Among them, nanoparticles (NPs) are one most versatile and promising tools. Here, we summarize characteristics NPs that facilitate penetration, including size, shape, chemical composition, surface charge, importantly, conjugation with various biological or synthetic molecules such glucose, transferrin, insulin, polyethylene glycol, peptides, aptamers. Additionally, discuss coating surfactants. A comprehensive overview common vitro vivo models NP penetration studies is also provided. The discussion extends discussing impairment under pathological conditions leveraging alterations delivery. Emphasizing need future uncover inherent properties NPs, review advocates role beyond systems calls efforts translating clinic therapeutics. Overall, stand out highly strategy precise targeting disorders.

Language: Английский

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Customizing delivery nano-vehicles for precise brain tumor therapy

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Jan. 28, 2023

Abstract Although some tumor has become a curable disease for many patients, involvement of the central nervous system (CNS) is still major concern. The blood–brain barrier (BBB), special structure in CNS, protects brain from bloodborne pathogens via its excellent properties and hinders new drug development tumor. Recent breakthroughs nanotechnology have resulted various nanovehicless (NPs) as carriers to cross BBB by different strategys. Here, complex compositions characteristics causes formation are elucidated exhaustively. Additionally, versatile nanovehicles with their recent applications pathways on delivery strategies overcome obstacle anti-brain briefly discussed. Customizing nanoparticles treatments proposed improve efficacy gut brain. This review provides broad perspective customizing nano-vehicles facilitate distribution across pave way creation innovative nanotechnology-based nanomaterials treatments.

Language: Английский

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Nanoparticles for Drug and Gene Delivery in Pediatric Brain Tumors’ Cancer Stem Cells: Current Knowledge and Future Perspectives

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(2), P. 505 - 505

Published: Feb. 2, 2023

Primary malignant brain tumors are the most common solid neoplasm in childhood. Despite recent advances, many children affected by aggressive or metastatic still present poor prognosis, therefore development of more effective therapies is urgent. Cancer stem cells (CSCs) have been discovered and isolated both pediatric adult patients with (e.g., medulloblastoma, gliomas ependymoma). CSCs a small clonal population cancer responsible for tumor initiation, maintenance progression, displaying resistance to conventional anticancer therapies. characterized specific repertoire surface markers intracellular pathways. These unique features biology offer opportunity build therapeutic approaches specifically target these complex bulk. Treatment classical chemotherapeutic regimen poses challenges location presence blood-brain barrier (BBB). Lastly, application chemotherapy developing followed long-term sequelae, especially on cognitive abilities. Novel avenues emerging panorama taking advantage nanomedicine. In this review we will summarize nanoparticle-based efficacy that NPs intrinsically demonstrated how they also decorated biomolecules. Furthermore, propose novel cargoes together advances nanoparticle design/synthesis final aim insidious

Language: Английский

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Transferrin receptor 1 targeted nanomedicine for brain tumor therapy

Biomaterials Science, Journal Year: 2023, Volume and Issue: 11(10), P. 3394 - 3413

Published: Jan. 1, 2023

This review summarizes the latest advances in TfR1-targeted nanomedicine for brain tumor therapy.

Language: Английский

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Comparative assessment of direct and indirect cold atmospheric plasma effects, based on helium and argon, on human glioblastoma: an in vitro and in vivo study

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Feb. 13, 2024

Recent research has highlighted the promising potential of cold atmospheric plasma (CAP) in cancer therapy. However, variations study outcomes are attributed to differences CAP devices and parameters, which lead diverse compositions products, including electrons, charged particles, reactive species, UV light, heat. This aimed evaluate compare optimal exposure time, duration, direction-dependent cellular effects two CAPs, based on argon helium gases, glioblastoma U-87 MG cells an animal model GBM. Two jets were used as low-temperature sources or gas was ionized by high voltage (4.5 kV) frequency (20 kHz). In vitro assessments human GBM normal astrocyte cell lines, using MTT assays, flow cytometry analysis, wound healing immunocytochemistry for Caspase3 P53 proteins, demonstrated that all studied jets, especially indirect CAP, selectively induced apoptosis, hindered tumor growth, inhibited migration. These occurred concurrently with increased intracellular levels oxygen species decreased total antioxidant capacity cells. vivo results further supported these findings, indicating single direct therapy, equal dose Temozolomide treatment, death a rat concurrent reduction size observed through PET-CT scan imaging significant increase survival rate. Additionally, there decrease GFAP protein levels, marker, expression immunohistochemical analyses. Furthermore, Ledge beam test analysis revealed general motor function improvement after similar treatment. Taken together, suggest holds great promise clinical applications

Language: Английский

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Nanoparticles for efficient drug delivery and drug resistance in glioma: New perspectives

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(5)

Published: May 1, 2024

Abstract Gliomas are the most common primary tumors of central nervous system, with glioblastoma multiforme (GBM) having highest incidence, and their therapeutic efficacy depends primarily on extent surgical resection postoperative chemotherapy. The role intracranial blood–brain barrier occurrence drug‐resistant gene O6‐methylguanine‐DNA methyltransferase have greatly limited chemotherapeutic agents in patients GBM made it difficult to achieve expected clinical response. In recent years, rapid development nanotechnology has brought new hope for treatment tumors. Nanoparticles (NPs) shown great potential tumor therapy due unique properties such as light, heat, electromagnetic effects, passive targeting. Furthermore, NPs can effectively load drugs, significantly reduce side effects improve efficacy, showing chemotherapy glioma. this article, we reviewed mechanisms glioma drug resistance, physicochemical NPs, advances resistance. We aimed provide perspectives

Language: Английский

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Breaking Barriers in Neuro-Oncology: A Scoping Literature Review on Invasive and Non-Invasive Techniques for Blood–Brain Barrier Disruption

Cancers, Journal Year: 2024, Volume and Issue: 16(1), P. 236 - 236

Published: Jan. 4, 2024

The blood–brain barrier (BBB) poses a significant challenge to drug delivery for brain tumors, with most chemotherapeutics having limited permeability into non-malignant tissue and only restricted access primary metastatic cancers. Consequently, due the drug’s inability effectively penetrate BBB, outcomes following chemotherapy continue be suboptimal. Several methods open BBB obtain higher concentrations in tumors have been proposed, selection of optimal method depending on size targeted tumor volume, chosen therapeutic agent, individual patient characteristics. Herein, we aim comprehensively describe osmotic disruption intra-arterial administration, intrathecal/intraventricular laser interstitial thermal therapy, convection-enhanced delivery, ultrasound methods, including high-intensity focused low-intensity as well tumor-treating fields. We explain scientific concept behind each method, preclinical/clinical research, advantages disadvantages, indications, potential avenues improvement. Given that has its limitations, it is unlikely future will rely single but rather synergistic effect combined approach. Disruption infusion or ultrasound, followed by drugs, promising Real-time monitoring necessary results.

Language: Английский

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Suppression of ITPKB degradation by Trim25 confers TMZ resistance in glioblastoma through ROS homeostasis

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 4, 2024

Abstract Temozolomide (TMZ) represents a standard-of-care chemotherapeutic agent in glioblastoma (GBM). However, the development of drug resistance constitutes significant hurdle treatment malignant glioma. Although specific innovative approaches, such as immunotherapy, have shown favorable clinical outcomes, inherent invasiveness most gliomas continues to make them challenging treat. Consequently, there is an urgent need identify effective therapeutic targets for overcome chemoresistance and facilitate development. This investigation used mass spectrometry examine proteomic profiles six pairs GBM patients who underwent surgery both primary recurrent tumors. A total 648 proteins exhibiting differential expression were identified. Gene Set Enrichment Analysis (GSEA) unveiled notable alterations pathways related METABOLISM_OF_LIPIDS BIOLOGICAL_OXIDATIONS between groups. Validation through glioma tissue arrays Xiangya cohort confirmed substantial upregulation inositol 1,4,5-triphosphate (IP3) kinase B (ITPKB) recurrence group, correlating with poor survival patients. In TMZ-resistant cells, depletion ITPKB led increase reactive oxygen species (ROS) NADPH oxidase (NOX) activity restored cell sensitivity TMZ. Mechanistically, decreased phosphorylation E3 ligase Trim25 at S100 position samples accounted weakened ubiquitination. This, turn, elevated stability impaired ROS production. Furthermore, or inhibitor GNF362 effectively TMZ xenograft mouse model. These findings reveal novel mechanism underlying propose promising target GBM.

Language: Английский

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Pathophysiological aspects of transferrin-A potential nano-based drug delivery signaling molecule in therapeutic target for varied diseases

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: March 4, 2024

Transferrin (Tf), widely known for its role as an iron-binding protein, exemplifies multitasking in biological processes. The of Tf iron metabolism involves both the uptake from by various cells, well endocytosis mediated complex and transferrin receptor (TfR). direct conjugation therapeutic compound immunotoxin studies using peptide or anti-Tf antibodies targeting moieties aims to prolong drug circulation time augment efficient cellular uptake, diminish systemic toxicity, traverse blood-brain barrier, restrict exposure, overcome multidrug resistance, enhance efficacy with disease specificity. This review primarily discusses actions Tf, development Tf-targeted nano-based delivery systems. goal is establish use a disease-targeting component, accentuating potential applications this protein.

Language: Английский

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