Brain Drug Delivery System Research Articles

Dose-Dependent Attenuation of the Efficacy of Clitoria ternatea by Cobalt Oxide Nanoparticles Against Diabetes-Induced Cognitive Impairment.

Diabetes mellitus is a metabolic disorder caused by insulin deficiency, insulin resistance, genetic alterations, and oxidative stress. The high glucose levels may impair the functioning of nerve cells, leading to neurodegenerative diseases, including cognitive impairment. Clitoria ternatea has various pharmacological activities, including antioxidant, anti-inflammatory, antidiabetic, and neuroprotective effects. The present study evaluates the efficacy of fresh flower aqueous extract of Clitoria ternatea against diabetes-induced cognitive impairment. The challenges in delivering drugs targeting the brain possess the limitations of crossing the blood-brain barrier. Metal nanoparticles are considered the most reliable brain drug delivery systems. Considering the neurotoxicity of cobalt oxide, whether it can be used to improve brain delivery is also evaluated. Cobalt oxide nanoparticles (Co3O4 NPs) of fresh flower aqueous extract of Clitoria ternatea are prepared by green synthesis and characterized. The effect of these nanoparticles is compared with Clitoria ternatea extract against Streptozotocin (STZ)-induced cognitive impairment. The behavioral, biochemical, in vivo antioxidant, total thiol content, estimation of proinflammatory cytokines, acetylcholine esterase, and nitrite levels in the brain of STZ-induced diabetic rats revealed that cobalt oxide nanoparticles showed neurotoxicity, whereas C. ternatea showed neuroprotective effect and also improved the cognitive function. The lower dose of cobalt oxide nanoparticles of C. ternatea (2mg/kg) exhibited a neuroprotective and cognition improvement effect. However, the higher dose (4mg/kg) of cobalt oxide nanoparticles of C. ternatea showed a neurotoxic effect. Since Co3O4 NPs are neuroprotective at low doses, they can be used for neuroprotective actions. However, dose optimization studies are required.

Virus-Shaped Mesoporous Silica Nanostars to Improve the Transport of Drugs across the Blood-Brain Barrier.

Conditions affecting the brain are the second leading cause of death globally. One of the main challenges for drugs targeting brain diseases is passing the blood-brain barrier (BBB). Here, the effectiveness of mesoporous silica nanostars (MSiNSs) with two different spike lengths to cross an in vitro BBB multicellular model was evaluated and compared to spherical nanoparticles (MSiNP). A modified sol-gel single-micelle epitaxial growth was used to produce MSiNS, which showed no cytotoxicity or immunogenicity at concentrations of up to 1 μg mL-1 in peripheral blood mononuclear and neuronal cells. The nanostar MSiNS effectively penetrated the BBB model after 24 h, and MSiNS-1 with a shorter spike length (9 ± 2 nm) crossed the in vitro BBB model more rapidly than the MSiNS-2 with longer spikes (18 ± 4 nm) or spherical MSiNP at 96 h, which accumulated in the apical and basolateral sides, respectively. Molecular dynamic simulations illustrated an increase in configurational flexibility of the lipid bilayer during contact with the MSiNS, resulting in wrapping, whereas the MSiNP suppressed membrane fluctuations. This work advances an effective brain drug delivery system based on virus-like shaped MSiNS for the treatment of different brain diseases and a mechanism for their interaction with lipid bilayers.

Nose to Brain Drug Delivery System

Abstract: The treatment of brain disorders is particularly challenging due to the presence of a variety of formidable obstacles to deliver drugs selectively and effectively to the brain. Blood-brainbarrier (BBB) constitutes the major obstacle to the uptake of drugs into the brain following systemic administration. Intranosedelivery offers a non-invasive and convenient method to bypass the BBB and delivery of therapeutics directly to the brain. The review discusses the potential of intranoseroute to deliver drugs to the brain, the mechanisms and pathways of direct nose to brain drug transport, the various factors influencing transnosedrug absorption, the conventional and novel intranosedrug delivery systems, the various intranosedrug delivery techniques and devices, and examples of brain drug transport that have been feasible in treating various brain disorders. Moreover, products on the market, investigational drugs, and the author’s perceptions about the prospect of intranosedelivery for treating brain disorders are also been discussed.

Formulation and In vitro Cytotoxicity Studies of Avastin Nanoparticle Mediated Targeted Nose to Brain Drug Delivery System

Nanoparticles (NPs) occupy a superior place among the recent approaches experimented to deliver drugs into brain by circumventing the BBB such as chemical modifications. The Emulsification PEG-PLGA nanoparticles carrying drug were made using the solvent evaporation method. In summary, PEG-PLGA was dissolved in acetone (50 mL) and PLGA was dissolved in PEG-PLGA (50:50, 7-11 mg/mL). The Chitosan-Avastin conjugates were created in the lab in accordance with the procedures and guidelines outlined in Chitosan (3.25 m mol) was hydrated in 1 N HCl, then the appropriate amount of distilled water was added. After adding NaOH (5N) to the reaction mixture to get the pH down to 5, Avastin (6.48 mmol) was added while the mixture was continuously stirred. In-vitro studies the basic aim is to check the effect of various drugs on various cancer cell lines. For testing purpose a large number of human cancer cell lines have been screened. Cells are cultivated in 96-well culture plates, and the rate of cell multiplication, which determines the rate of cell growth, is indirectly measured by the dye's color intensity, which is directly inversely proportional to the number of cells present. Using doses between 10 and 100 g/mL, the MTT test was performed to examine the cytotoxicity various polymer ratios and formulations on human lung cancer lines-A549. For the determination of the percentage of viability of various samples, the cancer cells without receiving therapy were utilized as the control.

Recent Approaches of Intranasal to Brain Drug Delivery System

While the intranasal administration of drugs to the brain has been gaining both research attention and regulatory success over the past several years, key fundamental and translational challenges remain to fully leveraging the promise of this drug delivery pathway for improving the treatment of various neurological and psychiatric illnesses. In response, this review highlights the current state of understanding of the nose-to-brain drug delivery pathway and how both biological and clinical barriers to drug transport using the pathway can been addressed, as illustrated by demonstrations of how currently approved intranasal sprays leverage these pathways to enable the design of successful therapies. Moving forward, aiming to better exploit the understanding of this fundamental pathway, we also outline the development of nanoparticle systems that show improvement in delivering approved drugs to the brain and how engineered nanoparticle formulations could aid in breakthroughs in terms of delivering emerging drugs and therapeutics while avoiding systemic adverse effects.

Biofabrication of nanovesicles for brain diseases.

Biofabrication of nanovesicles for brain diseases.

Stem Cell-derived Extracellular Vesicles: A Promising Nano Delivery Platform to the Brain?

A very important cause of the frustration with drug therapy for central nervous system (CNS) diseases is the failure of drug delivery. The blood-brain barrier (BBB) prevents most therapeutic molecules from entering the brain while maintaining CNS homeostasis. Scientists are keen to develop new brain drug delivery systems to solve this dilemma. Extracellular vesicles (EVs), as a class of naturally derived nanoscale vesicles, have been extensively studied in drug delivery due to their superior properties. This review will briefly present current brain drug delivery strategies, including invasive and non-invasive techniques that target the brain, and the application of nanocarriers developed for brain drug delivery in recent years, especially EVs. The cellular origin of EVs affects the surface protein, size, yield, luminal composition, and other properties of EVs, which are also crucial in determining whether EVs are useful as drug carriers. Stem cell-derived EVs, which inherit the properties of parental cells and avoid the drawbacks of cell therapy, have always been favored by researchers. Thus, in this review, we will focus on the application of stem cell-derived EVs for drug delivery in the CNS. Various nucleic acids, proteins, and small-molecule drugs are loaded into EVs with or without modification and undergo targeted delivery to the brain to achieve their therapeutic effects. In addition, the challenges facing the clinical application of EVs as drug carriers will also be discussed. The directions of future efforts may be to improve drug loading efficiency and precise targeting.

Development of Brain Drug Delivery System Using Intranasal Administration for the Treatment of Central Nervous System Diseases

Development of Brain Drug Delivery System Using Intranasal Administration for the Treatment of Central Nervous System Diseases

Innovative approach for nasal drug delivery system for brain target

The goal of brain drug targeting technology is the delivery of therapeutics across the blood brain barrier (BBB), including the human BBB. Nose to brain drug delivery has received a great deal of attention as a non- invasive, convenient and reliable drug delivery system. For the systemic and targetedadministration of drug. The various drug deliveries through some drug transport pathways, Factor influencing nasal drug absorption, formulation strategies nose to brain, colloidal carriers in nose to brain drug delivery system and nasal delivery systems. Physiological barriers (BBB) that restricts the delivery of drug to CNS. Thus intranasal route has attracted a wide attention of convenient, non-invasive, reliable, and safe route to achieve faster and higher level of drug in the brain through olfactory region by passing blood brain barrier. Intranasal administration rapid onset of action, no first –pass effect , no gastrointestinal degradation lungs toxicity and non-invasiveness application and also improves bioavailability.

Nose to Brain Drug Delivery System

The treatment of brain disorders is particularly challenging due to the presence of a variety of formidable obstacles to deliver drugs selectively and effectively to the brain. Blood-brain-barrier (BBB) constitutes the major obstacle to the uptake of drugs into the brain following systemic administration. An intranasal delivery provides some drugs with short channels to bypass the blood-brain barrier (BBB), especially for those with fairly low brain concentrations after a routine delivery, thus greatly enhancing the therapeutic effect on brain diseases. The nasal mucosa is nearby the brain, cerebrospinal fluid (CSF) and the drug concentrations can exceed plasma concentrations. a longer retention time at the nasal mucosal surface, penetration enhancement of the active through the nasal epithelia, and a reduction in drug metabolism in the nasal cavity. Indications where nose-to-brain products are likely to emerge first include the following: neurodegeneration, post-traumatic stress disorder, pain, and glioblastoma.

Special delEVery: Extracellular Vesicles as Promising Delivery Platform to the Brain.

The treatment of central nervous system (CNS) pathologies is severely hampered by the presence of tightly regulated CNS barriers that restrict drug delivery to the brain. An increasing amount of data suggests that extracellular vesicles (EVs), i.e., membrane derived vesicles that inherently protect and transfer biological cargoes between cells, naturally cross the CNS barriers. Moreover, EVs can be engineered with targeting ligands to obtain enriched tissue targeting and delivery capacities. In this review, we provide a detailed overview of the literature describing a natural and engineered CNS targeting and therapeutic efficiency of different cell type derived EVs. Hereby, we specifically focus on peripheral administration routes in a broad range of CNS diseases. Furthermore, we underline the potential of research aimed at elucidating the vesicular transport mechanisms across the different CNS barriers. Finally, we elaborate on the practical considerations towards the application of EVs as a brain drug delivery system.

High-gravity technology intensified Knoevenagel condensation-Michael addition polymerization of poly (ethylene glycol)-poly (n-butyl cyanoacrylate) for blood-brain barrier delivery

Poly (ethylene glycol)-poly (n-butyl cyanoacrylate) (PEG-PBCA) is a remarkable drug delivery carrier for permeating blood-brain barrier. In this work, a novel high-gravity procedure was reported to intensify Knoevenagel condensation-Michael addition polymerization of PEG-PBCA. A series of PEG-PBCA containing different block ratios were synthesized with narrow molecular weight distribution of polydispersity indexes less than 1.1. Furthermore, the reaction time reduced 60% compared to conventional stirred tank reactor process. Chemical structures of as-prepared polymers were characterized. In vitro drug delivery performance was evaluated. The cytotoxicity of PEG-PBCA to brain microvessel endothelial cells (BMVEC) decreases with the extension of the PEG chain and the shortening of the PBCA chain. The polymer cellular uptake to BMVECs was better after improving hydrophilicity by PEG block. Results of blood-brain barrier permeability demonstrated that medium length of PBCA chain and short PEG chain are favorable for hydrophobic Nile red permeation, while long PEG chain and short PBCA chain are beneficial to delivery water-soluble doxorubicin hydrochloride (Dox). The average apparent permeability coefficient increased 1.7 and 0.25 times than that of raw Nile red and Dox, respectively. High-gravity intensified condensation polymerization should have great potential in brain drug delivery system.

Recent Advances in the Use of Lipid-Based Nanoparticles Against Glioblastoma Multiforme.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. Although the overall incidence is less than 10 per 100,000 individuals, its poor prognosis and low survival rate make GBM a crucial public health issue. The main challenges for GBM treatment are related to tumor location and its complex and heterogeneous biology. In this sense, a broad range of nanoparticles with different sizes, architectures, and surface properties, have been engineered as brain drug delivery systems. Among them, lipid-based nanoparticles, such as liposomes, have been pointed out as promising materials to deliver antitumoral drugs to the central nervous system and thus, to improve brain drug targeting and therapeutic efficiency. Here, we describe the synthesis and general characteristics of lipid-based nanoparticles, as well as evidence in the past 5years regarding their potential use to treat GBM.

Alzheimer’s Disease and its Related Dementia Types: A Review on Their Management Via Nanotechnology Based Therapeutic Strategies

Dementia and its related types such as Alzheimer's disease, vascular dementia and mixed dementia belong to brain associated diseases, resulting in long-term progressive memory loss. These diseases are so severe that can affect a person's daily routine. Up to date, treatment of dementia is still an unmet challenge due to their complex pathophysiology and unavailable efficient pharmacological approaches. The use of nanotechnology based pharmaceutical products could possibly improve the management of dementia given that nanocarriers could more efficiently deliver drugs to the brain. The objective of this study is to provide the current nanotechnology based drug delivery systems for the treatment of various dementia types. In addition, the current diagnosis biomarkers for the mentioned dementia types along with their available pharmacological treatment are being discussed. An extensive review of the current nanosystems such as brain drug delivery systems against Alzheimer's disease, vascular dementia and mixed dementia was performed. Moreover, nanotheranostics as possible imaging markers for such dementias were also reported. The field of nanotechnology is quite advantageous for targeting dementia given that nanoscale drug delivery systems easily penetrate the blood brain barrier and circulate in the body for prolonged time. These nanoformulations consist of polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, microemulsions, nanoemulsions, and liquid crystals. The delivery of the nanotherapeutics can be achieved via various administration routes such as transdermal, injectable, oral, and more importantly, through the intranasal route. Nonetheless, the nanocarriers are mostly limited to Alzheimer's disease targeting; thus, nanocarriers for other types of dementia should be developed. To conclude, understanding the mechanism of neurodegeneration and reviewing the current drug delivery systems for Alzheimer's disease and other dementia types are significant for medical and pharmaceutical society to produce efficient therapeutic choices and novel strategies based on multifunctional and biocompatible nanocarriers, which can deliver the drug sufficiently into the brain.

Recent advances on drug delivery nanocarriers for cerebral disorders

Pharmacotherapies for brain disorders are generally faced with obstacles from the blood-brain barrier (BBB). There are a variety of drug delivery systems that have been put forward to cross or bypass the BBB with the access to the central nervous system. Brain drug delivery systems have benefited greatly from the development of nanocarriers, including lipids, polymers and inorganic materials. Consequently, various kinds of brain drug delivery nano-systems have been established, such as liposomes, polymeric nanoparticles (PNPs), nanomicelles, nanohydrogels, dendrimers, mesoporous silica nanoparticles and magnetic iron oxide nanoparticles. The characteristics of their carriers and preparations usually differ from each other, as well as their transportation mechanisms into intracerebral lesions. In this review, different types of brain drug delivery nanocarriers are classified and summarized, especially their significant achievements, to present several recommendations and directions for future strategies of cerebral delivery.

Nose to Brain Drug Delivery System: A Comprehensive Review

Nose to brain drug delivery system is an interesting approach to deliver a drug directly in the brain through the nose. Intranasal drug delivery is very beneficial because it avoids first-pass metabolism and achieves a greater concentration of drugs in the central nervous system (CNS) at a low dose. This delivery system is used for the treatment of various neurological disorders such as Parkinson's disease, Alzheimer's disease, schizophrenia, dementia, brain cancer, etc. To treat such types of diseases, different formulations like nanoparticles (NPs), microemulsions, in situ gel, etc. can be used depending on the physiochemical properties of the drug. In this review, some essential characteristics related to the delivery of nose to the brain and their possible obstacles are underlined, which include anatomy and physiology of nose to brain delivery. This review also summarizes innovations from the past three to five years.

Lipid Nanoparticles Improve the Uptake of α-Asarone Into the Brain Parenchyma: Formulation, Characterization, In Vivo Pharmacokinetics, and Brain Delivery.

Treatment of brain-related diseases is one of the most strenuous challenges in drug delivery research due to numerous hurdles, including poor blood-brain barrier penetration, lack of specificity, and severe systemic toxicities. Our research primarily focuses on the delivery of natural therapeutic compound, α-asarone, for the treatment of brain-related diseases. However, α-asarone has poor aqueous solubility, bioavailability, and stability, all of which are critical issues that need to be addressed. This study aims at formulating a lipid nanoparticulate system of α-asarone (A-LNPs) that could be used as a brain drug delivery system. The physicochemical, solid-state properties, stability, and in vitro and in vivo studies of the A-LNPs were characterized. The release of α-asarone from the A-LNPs was prolonged and sustained. After intravenous administration of A-LNPs or free α-asarone, significantly higher levels of α-asarone from the A-LNPs were detected in murine plasma and brain parenchyma fractions, confirming the ability of A-LNPs to not only maintain a therapeutic concentration of α-asarone in the plasma, but also transport α-asarone across the blood-brain barrier. These findings confirm that lipid nanoparticulate systems enable penetration of natural therapeutic compound α-asarone through the blood-brain barrier and may be a candidate for the treatment of brain-related diseases.

Targeting the brain: various approaches and science involved

The brain targeting drug delivery system is the technique and process to deliver the drug into brain or central nerves system (CNS). The main problem arise during brain targeting in case of several brain related diseases and disorders such as CNS malignancy, brain abscess, multiple sclerosis, schizophrenia etc. selective and limiting permeation nature of barriers i.e. blood brain barrier (BBB) and blood cerebrospinal fluid barrier (BCSF), these two barriers only allow highly lipophilic molecule enters into brain and is one of the greatest clinical impediment of treatment of brain and CNS diseases and disorders. To treated this type of diseases and disorders drugs are targeted into brain and drug must be cross these two barriers they’re by different types of approaches are used to delivered drug molecules.Aim of research. The main aim of this review paper is to compile all the approaches, strategies and techniques used for brain targeted drug delivery in a single paper/ article.Material and method. To prepare this manuscript, various keywords were searched in different engines such as Google, Yahoo and Bing etc. The available information in public domain was collected and classified according to brain drug delivery system. This review deals with approaches and current strategies used to enhance the brain targeted drug delivery system. The approaches for brain targeting – invasive, non- invasive and miscellaneous techniques, by using these approaches enhance the drugs delivery and drugs are easily across BBB and BCSF.Result. The different type of approaches and strategies used to enhance the drug delivery into brain and CNS. All these techniques described in this paper are applied for overcoming the problems that arises during treatment of brain related diseases. This review paper has a list of different types of models (In-vitro and In-vivo) used in study of brain and CNS drug delivery.Conclusions. Drug delivery to brain for treating a various diseases and disorders are very difficult and challenging because the delivery of drug molecules must be pass through the BBB and BCSF. Overcome this difficulties and challenges certain approaches and technique such as invasive, non-invasive, intranasal delivery of drug, ocular delivery of drug and focused ultrasound technique are used to brain targeting. They are help to penetrate the drug molecule through BBB and CSF very easily and enhance the efficacy of treatment. This review article covered current approaches and strategies of brain targeting drug delivery in past five to ten years. These approaches and strategies are used to the brain delivery of drug, proteins, peptides, amino acids, etc.

Development of brain drug delivery system using intranasal administration for the treatment of central nervous system diseases

Development of brain drug delivery system using intranasal administration for the treatment of central nervous system diseases

PLGA-PEG-ANG-2 Nanoparticles for Blood-Brain Barrier Crossing: Proof-of-Concept Study.

The treatment of diseases that affect the central nervous system (CNS) represents a great research challenge due to the restriction imposed by the blood–brain barrier (BBB) to allow the passage of drugs into the brain. However, the use of modified nanomedicines engineered with different ligands that can be recognized by receptors expressed in the BBB offers a favorable alternative for this purpose. In this work, a BBB-penetrating peptide, angiopep-2 (Ang–2), was conjugated to poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles through pre- and post-formulation strategies. Then, their ability to cross the BBB was qualitatively assessed on an animal model. Proof-of-concept studies with fluorescent and confocal microscopy studies highlighted that the brain-targeted PLGA nanoparticles were able to cross the BBB and accumulated in neuronal cells, thus showing a promising brain drug delivery system.