Convolutions in the rendition of nose to brain therapeutics from bench to bedside: Feats &amp; fallacies

Goel, Honey; Kalra, Vinni; Verma, Sant Kumar; Dubey, Sunil Kumar; Tiwary, Ashok K.

doi:10.1016/j.jconrel.2021.12.009

Cited by 26 publications

(14 citation statements)

References 299 publications

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“…The olfactory epithelium serves as the main facilitator for the transfer of molecules to the brain and covers only 3% of the nasal cavity in humans, compared to 50% in rodents [42]. In addition, mild anesthesia may lower the velocity of inhaled droplets and increase contact with the nasal mucosa [13]. The permeation enhancer applied would promote the transportation from the nasal mucosa to OB.…”

Section: Discussionmentioning

confidence: 99%

“…Intranasal delivery is a noninvasive and direct route from the nose to the brain, which largely bypasses BBB and the first-pass metabolism [13]. In recent years, there has been a surge in studies exploring the combination of sEVs treatment with intranasal administration in various fields of CNS disorders and harvesting promising therapeutic effects [14][15][16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

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Rapid and Widespread Distribution of Intranasal Small Extracellular Vesicles Derived from Mesenchymal Stem Cells throughout the Brain Potentially via the Perivascular Pathway

Shen,

You,

et al. 2023

Pharmaceutics

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Intranasal administration is a promising strategy to enhance the delivery of the sEVsomes-based drug delivery system to the central nervous system (CNS). This study aimed to explore central distributive characteristics of mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) and underlying pathways. Here, we observed that intranasal MSC-sEVs were rapidly distributed to various brain regions, especially in the subcortex distant from the olfactory bulb, and were absorbed by multiple cells residing in these regions. We captured earlier transportation of intranasal MSC-sEVs into the perivascular space and found an increase in cerebrospinal fluid influx after intranasal administration, particularly in subcortical structures of anterior brain regions where intranasal sEVs were distributed more significantly. These results suggest that the perivascular pathway may underlie the rapid and widespread central delivery kinetics of intranasal MSC-sEVs and support the potential of the intranasal route to deliver MSC-sEVs to the brain for CNS therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rapid and Widespread Distribution of Intranasal Small Extracellular Vesicles Derived from Mesenchymal Stem Cells throughout the Brain Potentially via the Perivascular Pathway

Shen,

You,

et al. 2023

Pharmaceutics

View full text Add to dashboard Cite

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“… 14 The outermost nasal cavity is the vestibule (0.6 cm 2 ), which is lined by keratinized and stratified squamous epithelium with embedded vibrissa. 22 , 23 The vestibule filters foreign substances larger than 10 µm via the mucus layer covering the surface of the vibrissa. The vestibule exhibits low drug permeability because of the keratinized squamous epithelium.…”

Section: Nose-to-brain Drug Delivery Systemsmentioning

confidence: 99%

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

Koo,

Lim,

2024

IJN

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

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“…Majority of hydrophilic compounds are unable to cross the BBB, owing to the presence of the efflux transporters like P-glycoprotein (P-gp) and other multi-drug-related protein transporters ( Matsumoto et al, 2017 ; Patel et al, 2018 ). Due to their poor ability to cross the BBB, high first-pass effect, and frequent off-site targeting ( Goel et al, 2022 ), and prospective peptide-based ( Ayyalasomayajula and Suresh, 2018 ; Trapani et al, 2018 ) or gene delivery ( Malhotra et al, 2013 )-based therapies continue to be in the translational phase ( Goel, et al, 2022 ).…”

Section: Alzheimer’s Diseasementioning

confidence: 99%

Nasal delivery of neurotherapeutics via nanocarriers: Facets, aspects, and prospects

Rajput

Dhapte‐Pawar

2022

Front. Pharmacol.

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Alzheimer’s disease (AD) is one of the neurological ailments which continue to represent a major public health challenge, owing to increased life expectancy and aging population. Progressive memory loss and decrease in cognitive behavior, owing to irreversible destruction of neurons along with expensive therapeutic interventions, call for an effective, alternate, yet affordable treatment for Alzheimer’s disease. Safe and effective delivery of neurotherapeutics in Alzheimer’s like central nervous system (CNS) disorders still remains elusive despite the major advances in both neuroscience and drug delivery research. The blood–brain barrier (BBB) with its tight endothelial cell layer surrounded by astrocyte foot processes poses as a major barrier for the entry of drugs into the brain. Nasal drug delivery has emerged as a reliable method to bypass this blood–brain barrier and deliver a wide range of neurotherapeutic agents to the brain effectively. This nasal route comprises the olfactory or trigeminal nerves originating from the brain and terminating into the nasal cavity at the respiratory epithelium or olfactory neuroepithelium. They represent the most direct method of noninvasive entry into the brain, opening the most suitable therapeutic avenue for treatment of neurological diseases. Also, drugs loaded into nanocarriers can have better interaction with the mucosa that assists in the direct brain delivery of active molecules bypassing the BBB and achieving rapid cerebrospinal fluid levels. Lipid particulate systems, emulsion-based systems, vesicular drug delivery systems, and other nanocarriers have evolved as promising drug delivery approaches for the effective brain delivery of anti-Alzheimer’s drugs with improved permeability and bioavailability via the nasal route. Charge, size, nature of neurotherapeutics, and formulation excipients influence the effective and targeted drug delivery using nanocarriers via the nasal route. This article elaborates on the recent advances in nanocarrier-based nasal drug delivery systems for the direct and effective brain delivery of the neurotherapeutic molecules. Additionally, we have attempted to highlight various experimental strategies, underlying mechanisms in the pathogenesis and therapy of central nervous system diseases, computational approaches, and clinical investigations pursued so far to attain and enhance the direct delivery of therapeutic agents to the brain via the nose-to-brain route, using nanocarriers.

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Convolutions in the rendition of nose to brain therapeutics from bench to bedside: Feats & fallacies

Cited by 26 publications

References 299 publications

Rapid and Widespread Distribution of Intranasal Small Extracellular Vesicles Derived from Mesenchymal Stem Cells throughout the Brain Potentially via the Perivascular Pathway

Rapid and Widespread Distribution of Intranasal Small Extracellular Vesicles Derived from Mesenchymal Stem Cells throughout the Brain Potentially via the Perivascular Pathway

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

Nasal delivery of neurotherapeutics via nanocarriers: Facets, aspects, and prospects

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