A Method to Prepare a Bioprobe for Regulatory Science of the Drug Delivery System to the Brain: An Angulin Binder to Modulate Tricellular Tight Junction-Seal

2020 ◽  
Author(s):  
Keisuke Tachibana ◽  
Masuo Kondoh
Keyword(s):  
Drug Delivery ◽  
Tight Junction ◽  
Drug Delivery System ◽  
Delivery System ◽  
Regulatory Science ◽  
The Brain

Management of Glioblastoma Multiforme by Phytochemicals: Applications of Nanoparticle Based Targeted Drug Delivery System

2020 ◽  
Vol 21 ◽  
Author(s):  
Sayed Md Mumtaz ◽  
Gautam Bhardwaj ◽  
Shikha Goswami ◽  
Rajiv Kumar Tonk ◽  
Ramesh K. Goyal ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Glioblastoma Multiforme ◽  
Drug Delivery System ◽  
Delivery System ◽  
Genetic Disorder ◽  
Drug Regimen ◽  
Brain Regions ◽  
Radio Therapy ◽  
Novel Drug ◽  
The Brain

: The Glioblastoma Multiforme (GBM; grade IV astrocytoma) exhort tumor of star-shaped glial cell in the brain. It is a fast-growing tumor that spreads to nearby brain regions specifically to cerebral hemispheres in frontal and temporal lobes. The etiology of GBM is unknown, but major risk factors are genetic disorder like neurofibromatosis and schwanomatosis which develop the tumor in the nervous system. The management of GBM with chemo-radio therapy leads to resistance and current drug regimen like Temozolomide (TMZ) is less efficacious. The reasons behind failure of drugs are due to DNA alkylation in cell cycle by enzyme DNA guanidase and mitochondrial dysfunction. Naturally occurring bio-active compounds from plants known as phytochemicals, serve as vital sources for anti-cancer drugs. Some typical examples include taxol analogs, vinca alkaloids such as vincristine, vinblastine, podophyllotoxin analogs, camptothecin, curcumin, aloe emodin, quercetin, berberine e.t.c. These phytochemicals often act via regulating molecular pathways which are implicated in growth and progression of cancers. However the challenges posed by the presence of BBB/BBTB to restrict passage of these phytochemicals, culminates in their low bioavailability and relative toxicity. In this review we integrated nanotech as novel drug delivery system to deliver phytochemicals from traditional medicine to the specific site within the brain for the management of GBM.

Identification and Design of Peptides as a New Drug Delivery System for the Brain

2007 ◽  
Vol 324 (3) ◽  
pp. 1064-1072 ◽  
Author(s):  
Michel Demeule ◽  
Anthony Régina ◽  
Christian Ché ◽  
Julie Poirier ◽  
Tran Nguyen ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
New Drug ◽  
The Brain

Carbon Nano Tubes: Novel drug delivery system in amelioration of Alzheimer’s disease

2020 ◽  
Vol 23 ◽  
Author(s):  
Jayanti Mishra ◽  
Bhumika Kumar ◽  
Mukesh Pandey ◽  
Faheem Hyder Pottoo ◽  
Faizana Fayaz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Carbon Nanotubes ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Drug Delivery System ◽  
Delivery System ◽  
Drug Loading ◽  
Brain Disorder ◽  
Biological Barriers ◽  
The Brain

Background: Alzheimer’s disease is an irreversible, progressive brain disorder manifested with symptoms like loss of memory (known as dementia), personality changes, loss of cognition, impaired movement, confusion, deteriorated planning and thought process. Neurodegeneration in Alzheimer’s disease is the result of deposition of protein beta-amyloid that forms plaques and another protein called tau, forming tangles that prevent proper functioning of nerve cells in the brain. Methods: The goal of the review was to comprehensively study the utilization of nanotechnology and the role that carbon nanotubes can play as a drug delivery system for amelioration of Alzheimer’s disease. Results: Nanotechnology is one of the most researched domains of modern science. It contributes significantly to therapeutics by facilitating drug therapy to reach the target sites, which are otherwise difficult to reach with conventional drug delivery systems. Carbon nanotubes are the allotropes of carbon in which several carbon atoms bind with each other to form a cylindrical or a tube-like structure. The carbon nanotubes possess several unique qualities, which confers them with a high potential of being utilized as an efficient drug delivery system. They offer high drug loading, can readily cross the toughest biological barriers like BBB. Carbon nanotubes also facilitate the passage of drugs to the brain via the olfactory route, which further helps in restoring normal autophagy, thus preventing the elimination of autophagic chemicals. They can carry a vast range of cargos, including drugs, antigens, genetic materials, and biological macromolecules. Conclusion: Carbon nanotubes are highly promising drug delivery system for anti-Alzheimer’s drugs. They have potential of overcoming the various biological barriers like BBB. However, more extensive research is required so as to set up a firm base for development of advanced commercial products based on carbon nanotubes for treatment of Alzheimer’s disease.

Nose to Brain Drug Delivery System: A Comprehensive Review

2020 ◽  
Vol 10 (4) ◽  
pp. 288-299
Author(s):  
Pankaj Kumar ◽  
Varun Garg ◽  
Neeraj Mittal
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Anatomy And Physiology ◽  
Brain Drug Delivery ◽  
System A ◽  
Interesting Approach ◽  
The Central Nervous System ◽  
The Brain

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.

Nanoparticlized System: Promising Approach for the Management of Alzheimer’s Disease through Intranasal Delivery

2020 ◽  
Vol 26 (12) ◽  
pp. 1331-1344
Author(s):  
Shiv Bahadur ◽  
Nidhi Sachan ◽  
Ranjit K. Harwansh ◽  
Rohitas Deshmukh
Keyword(s):  
Alzheimer’S Disease ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Drug Delivery System ◽  
Delivery System ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Limiting Factor ◽  
Nasal Drug Delivery ◽  
The Brain

Alzheimer's disease (AD) is a neurodegenerative brain problem and responsible for causing dementia in aged people. AD has become most common neurological disease in the elderly population worldwide and its treatment remains still challengeable. Therefore, there is a need of an efficient drug delivery system which can deliver the drug to the target site. Nasal drug delivery has been used since prehistoric times for the treatment of neurological disorders like Alzheimer's disease (AD). For delivering drug to the brain, blood brain barrier (BBB) is a major rate limiting factor for the drugs. The desired drug concentration could not be achieved through the conventional drug delivery system. Thus, nanocarrier based drug delivery systems are promising for delivering drug to brain. Nasal route is a most convenient for targeting drug to the brain. Several factors and mechanisms need to be considered for an effective delivery of drug to the brain particularly AD. Various nanoparticlized systems such as nanoparticles, liposomes, exosomes, phytosomes, nanoemulsion, nanosphere, etc. have been recognized as an effective drug delivery system for the management of AD. These nanocarriers have been proven with improved permeability as well as bioavailability of the anti-Alzheimer’s drugs. Some novel drug delivery systems of anti-Alzheimer drugs are under investigation of different phase of clinical trials. Present article highlights on the nanotechnology based intranasal drug delivery system for the treatment of Alzheimer’s disease. Furthermore, consequences of AD, transportation mechanism, clinical updates and recent patents on nose to brain delivery for AD have been discussed.

The Two Faces of Exosomes in Parkinson’s Disease: From Pathology to Therapy

2021 ◽  
pp. 107385842199000
Author(s):  
Maria Izco ◽  
Estefania Carlos ◽  
Lydia Alvarez-Erviti
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Drug Delivery System ◽  
Glial Cells ◽  
Delivery System ◽  
Alpha Synuclein ◽  
Macromolecular Drugs ◽  
The Brain

Accumulating evidence suggests that exosomes play a key role in Parkinson’s disease (PD). Exosomes may contribute to the PD progression facilitating the spread of pathological alpha-synuclein or activating immune cells. Glial cells also release exosomes, and transmission of exosomes derived from activated glial cells containing inflammatory mediators may contribute to the propagation of the neuroinflammatory response. Glia-to-neuron transmission of exosomes containing alpha-synuclein may contribute to alpha-synuclein propagation and neurodegeneration. Additionally, miRNAs can be transmitted among cells via exosomes inducing changes in the genetic program of the target cell contributing to PD progression. Exosomes also represent a promising drug delivery system. The brain is a difficult target for drugs of all classes because the blood-brain barrier excludes most macromolecular drugs. One of the major challenges is the development of vehicles for robust delivery to the brain. Targeted exosomes may have the potential for delivering therapeutic agents, including proteins and gene therapy molecules, into the brain. This review summarizes recent advances in the role of exosomes in PD pathology progression and their potential use as drug delivery system for PD treatment, the two faces of the exosomes in PD.

scholarly journals Improved Safety and Anti-Glioblastoma Efficacy of CAT3-Encapsulated SMEDDS through Metabolism Modification

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 484
Author(s):  
Hongliang Wang ◽  
Lin Li ◽  
Jun Ye ◽  
Wujun Dong ◽  
Xing Zhang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Gastrointestinal Tract ◽  
Side Effects ◽  
Drug Delivery System ◽  
Delivery System ◽  
Lymphatic Transport ◽  
Pharmacokinetic Parameters ◽  
Gastrointestinal Side Effects ◽  
The Brain

13a-(S)-3-pivaloyloxyl-6,7-dimethoxyphenanthro(9,10-b)-indolizidine (CAT3) is a novel oral anti-glioma pro-drug with a potent anti-tumor effect against temozolomide-resistant glioma. 13a(S)-3-hydroxyl-6,7-dimethoxyphenanthro(9,10-b)-indolizidine (PF403) is the active in vivo lipase degradation metabolite of CAT3. Both CAT3 and PF403 can penetrate the blood–brain barrier to cause an anti-glioma effect. However, PF403, which is produced in the gastrointestinal tract and plasma, causes significant gastrointestinal side effects, limiting the clinical application of CAT3. The objective of this paper was to propose a metabolism modification for CAT3 using a self-microemulsifying drug delivery system (SMEDDS), in order to reduce the generation of PF403 in the gastrointestinal tract and plasma, as well as increase the bioavailability of CAT3 in vivo and the amount of anti-tumor substances in the brain. Thus, a CAT3-loaded self-microemulsifying drug delivery system (CAT3-SMEDDS) was prepared, and its physicochemical characterization was systematically carried out. Next, the pharmacokinetic parameters of CAT3 and its metabolite in the rats’ plasma and brain were measured. Furthermore, the in vivo anti-glioma effects and safety of CAT3-SMEDDS were evaluated. Finally, Caco-2 cell uptake, MDCK monolayer cellular transfer, and the intestinal lymphatic transport mechanisms of SMEDDS were investigated in vitro and in vivo. Results show that CAT3-SMEDDS was able to form nanoemulsion droplets in artificial gastrointestinal fluid within 1 min, displaying an ideal particle size (15–30 nm), positive charge (5–9 mV), and controlled release behavior. CAT3-SMEDDS increased the membrane permeability of CAT3 by 3.9-fold and promoted intestinal lymphatic transport. Hence, the bioavailability of CAT3 was increased 79% and the level of its metabolite, PF403, was decreased to 49%. Moreover, the concentrations of CAT3 and PF403 were increased 2–6-fold and 1.3–7.2-fold, respectively, in the brain. Therefore, the anti-glioma effect in the orthotopic models was improved with CAT3-SMEDDS compared with CAT3 in 21 days. Additionally, CAT3-SMEDDS reduced the gastrointestinal side effects of CAT3, such as severe diarrhea, necrosis, and edema, and observed less inflammatory cell infiltration in the gastrointestinal tract, compared with the bare CAT3. Our work reveals that, through the metabolism modification effect, SMEDDS can improve the bioavailability of CAT3 and reduce the generation of PF403 in the gastrointestinal tract and plasma. Therefore, it has the potential to increase the anti-glioma effect and reduce the gastrointestinal side effects of CAT3 simultaneously.

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