Nanotherapeutics for Nose-to-Brain Drug Delivery: An Approach to Bypass the Blood Brain Barrier

Lee, David; Minko, Tamara

doi:10.3390/pharmaceutics13122049

Cited by 75 publications

(64 citation statements)

References 265 publications

(301 reference statements)

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“…However, smaller carbon-based particles less than 20 nm, such as quantum dots (QDs), showed increased accumulation in the brain parenchyma [ 31 ]. The QDs can pass through the BBB pathway and through the trigeminal nerve or olfactory epithelium, which can cause additional problems when investigating in vivo toxicity [ 32 , 33 ]. However, despite the accumulation of carbon-based particles in organs, due to their chemical makeup, carbon-based NPs typically display little to no significant increase in toxicity when examined in vivo [ 34 ]; however, some toxic effects have been recorded [ 35 ].…”

Section: Current Methods and Concerns For In Vivo Nanotoxicity Determ...mentioning

confidence: 99%

Analysis of Nanomaterials on Biological and Environmental Systems and New Analytical Methods for Improved Detection

Reagen

Zhao

2022

IJMS

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The advancing field of nanoscience has produced lower mass, smaller size, and expanded chemical composition nanoparticles over recent years. These new nanoparticles have challenged traditional analytical methods of qualification and quantification. Such advancements in nanoparticles and nanomaterials have captured the attention of toxicologists with concerns regarding the environment and human health impacts. Given that nanoparticles are only limited by size (1–100 nm), their chemical and physical characteristics can drastically change and thus alter their overall nanotoxicity in unpredictable ways. A significant limitation to the development of nanomaterials is that traditional regulatory and scientific methods used to assess the biological and environmental toxicity of chemicals do not generally apply to the assessment of nanomaterials. Significant research effort has been initiated, but much more is still needed to develop new and improved analytical measurement methods for detecting and quantitating nanomaterials in biological and environmental systems.

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Section: Current Methods and Concerns For In Vivo Nanotoxicity Determ...mentioning

confidence: 99%

Analysis of Nanomaterials on Biological and Environmental Systems and New Analytical Methods for Improved Detection

Reagen

Zhao

2022

IJMS

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“…Biocompatible lipid particulate systems are made using biodegradable lipids which make them more biocompatible physiologically with less probability for toxicity. Types of lipids such as 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), poloxamers, cholesterol, polyethylene glycol (PEG), capmul MCM, precirol, lecithin, and compritol 888 ATO along with the size and charge on lipid excipients have a profound impact on the nose-to-brain delivery of neurotherapeutic drugs ( Lee and Minko, 2021 ). Positively charged lipid carriers are found to have an effective intranasal delivery than neutral or anionic charged lipid carriers as they are easily attracted by the anionic endothelial cells of the brain via absorptive mediated transport.…”

Section: Nanocarrier-based Systems For Management Of Alzheimer’s Dise...mentioning

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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“…During recent years, intranasal (IN) administration, a non-invasive drug delivery approach for local or systemic effects, has been used to provide direct nose-to-brain transport. Due to the presence of direct anatomical connection between the CNS and the nasal cavity, IN administration can provide the access of drugs to the CNS [ 8 , 9 , 10 , 11 ]. As compared to parenteral administration, IN delivery can overcome the BBB, provide faster brain delivery, and enhance drug targeting and drug bioavailability.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Intranasal Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Nose-to-Brain Delivery

Nguyen

Maeng

2022

Pharmaceutics

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Nose-to-brain drug delivery has been of great interest for the treatment of many central nervous system (CNS) diseases and psychiatric disorders over past decades. Several nasally administered formulations have been developed to circumvent the blood-brain barrier and directly deliver drugs to the CNS through the olfactory and trigeminal pathways. However, the nasal mucosa’s drug absorption is insufficient and the volume of the nasal cavity is small, which, in combination, make nose-to-brain drug delivery challenging. These problems could be minimized using formulations based on solid lipid nanoparticles (SLNs) or nanostructured lipid carriers (NLCs), which are effective nose-to-brain drug delivery systems that improve drug bioavailability by increasing drug solubility and permeation, extending drug action, and reducing enzymatic degradation. Various research groups have reported in vivo pharmacokinetics and pharmacodynamics of SLNs and NLCs nose-to-brain delivery systems. This review was undertaken to provide an overview of these studies and highlight research performed on SLN and NLC-based formulations aimed at improving the treatment of CNS diseases such neurodegenerative diseases, epilepsy, and schizophrenia. We discuss the efficacies and brain targeting efficiencies of these formulations based on considerations of their pharmacokinetic parameters and toxicities, point out some gaps in current knowledge, and propose future developmental targets.

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Nanotherapeutics for Nose-to-Brain Drug Delivery: An Approach to Bypass the Blood Brain Barrier

Cited by 75 publications

References 265 publications

Analysis of Nanomaterials on Biological and Environmental Systems and New Analytical Methods for Improved Detection

Analysis of Nanomaterials on Biological and Environmental Systems and New Analytical Methods for Improved Detection

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

Pharmacokinetics and Pharmacodynamics of Intranasal Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Nose-to-Brain Delivery

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