scholarly journals Intranasal Administration as a Route to Deliver Drugs to the Brain (Review)

2021 ◽  
Vol 10 (4) ◽  
pp. 117-127
Author(s):  
N. N. Porfiryeva ◽  
I. I. Semina ◽  
R. I. Moustafine ◽  
V. V. Khutoryanskiy
Keyword(s):  
Phase Transition ◽  
Drug Delivery ◽  
Intranasal Administration ◽  
Proteolytic Enzymes ◽  
Rapid Onset ◽  
The Body ◽  
Brain Diseases ◽  
External Stimulation ◽  
In Situ Gelling ◽  
The Brain

Introduction. Intranasal drug delivery from nose-to-brain is one of the promising approaches for the treatment of brain diseases including neurodegenerative diseases, stroke, brain tumors, etc.Text. Delivery of drugs through the nose has a number of advantages, including the rapid onset of a pharmacological effect, the ability to bypass the blood-brain barrier, avoidance of some side effects and fast and non-invasive route of administration. However, the significant disadvantages of this route are rapid elimination of the drug from the surface of the mucosal membrane, poor penetration of the drug through the nasal mucosa, mucociliary clearance and effects of proteolytic enzymes. Currently, to overcome the above limitations, various approaches are used, including the development of delivery systems from nose-to-brain, which are mucoadhesive, mucus-penetrating and gel-forming systems that facilitate the retention or penetration of drugs through the mucosal membranes. At the same time, high-molecular weight compounds play a significant role in the design of these systems. In particular, mucoadhesive systems can be prepared from cationic and anionic polymers. Recent studies have also shown that interpolyelectrolyte complexes also exhibit mucoadhesive properties. An improvement in mucoadhesive properties of polymers can also be achieved by conjugating various functional groups such as thiols, maleimides, acrylates, methacrylates, catechols, etc. Mucus-penetrating systems can be prepared by PEGylation of nanoparticles, as well as functionalization with some poly(2-oxazolines), polyvinyl alcohol, etc. The mucus-penetrating ability of these polymers has been shown in other mucosal membranes in the body. Finally, increased penetration can be achieved by using mucolytic agents in combination with non-ionic surfactants. Another approach to increase the efficiency of drug delivery from nose-to-brain is the use of in situ gelling systems. Initially, this type of formulation exists as a solution; then a phase transition to gel is observed in response to chemical and physical effects. Depending on the external stimulation of the phase transition, thermo-, pH-, ion-reversible and other systems are known. These systems have shown effectiveness for delivery to the brain by intranasal administration.Conclusion. Effective intranasal delivery of drugs and therapeutic agents to the brain can be achieved by using mucoadhesive, mucus-penetrating, gelling systems and/or their combinations.

Alzheimer’s disease and its related Dementia types: A review on their management via nanotechnology based therapeutic strategies

2021 ◽  
Vol 18 ◽  
Author(s):  
Panoraia I. Siafaka ◽  
Gökce Mutlu ◽  
Neslihan Üstündağ Okur
Keyword(s):  
Alzheimer’S Disease ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Vascular Dementia ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
The Body ◽  
Daily Routine ◽  
Mixed Dementia ◽  
The Brain

Background: 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 de- mentias 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. Objective: 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 dis- cussed. Method: 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, nan- otheranostics as possible imaging markers for such dementias were also reported. Results: 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, nanostruc- tured lipid carriers, microemulsions, nanoemulsions, and liquid crystals. The delivery of the nan- otherapeutics 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. Conclusion: To conclude, understanding the mechanism of neurodegeneration and reviewing the cur- rent 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 mul- tifunctional and biocompatible nanocarriers, which can deliver the drug sufficiently into the brain.

scholarly journals The vascular basement membrane in the healthy and pathological brain

2017 ◽  
Vol 37 (10) ◽  
pp. 3300-3317 ◽  
Author(s):  
Maj S Thomsen ◽  
Lisa J Routhe ◽  
Torben Moos
Keyword(s):  
Drug Delivery ◽  
Basement Membrane ◽  
Proteolytic Enzymes ◽  
Three Dimensional ◽  
Matrix Proteins ◽  
Vascular Basement Membrane ◽  
Capillary Endothelial Cells ◽  
The Brain ◽  
Astrocyte Endfeet

The vascular basement membrane contributes to the integrity of the blood-brain barrier (BBB), which is formed by brain capillary endothelial cells (BCECs). The BCECs receive support from pericytes embedded in the vascular basement membrane and from astrocyte endfeet. The vascular basement membrane forms a three-dimensional protein network predominantly composed of laminin, collagen IV, nidogen, and heparan sulfate proteoglycans that mutually support interactions between BCECs, pericytes, and astrocytes. Major changes in the molecular composition of the vascular basement membrane are observed in acute and chronic neuropathological settings. In the present review, we cover the significance of the vascular basement membrane in the healthy and pathological brain. In stroke, loss of BBB integrity is accompanied by upregulation of proteolytic enzymes and degradation of vascular basement membrane proteins. There is yet no causal relationship between expression or activity of matrix proteases and the degradation of vascular matrix proteins in vivo. In Alzheimer’s disease, changes in the vascular basement membrane include accumulation of Aβ, composite changes, and thickening. The physical properties of the vascular basement membrane carry the potential of obstructing drug delivery to the brain, e.g. thickening of the basement membrane can affect drug delivery to the brain, especially the delivery of nanoparticles.

scholarly journals Interplay of Good Bacteria and Central Nervous System: Cognitive Aspects and Mechanistic Considerations

2021 ◽  
Vol 15 ◽  
Author(s):  
Mahmoud Salami
Keyword(s):  
Gut Microbiota ◽  
Cognitive Processing ◽  
Clinical Problem ◽  
The Body ◽  
Brain Diseases ◽  
Normal Brain ◽  
Beneficial Effects ◽  
Normal Brain Function ◽  
The Brain ◽  
Common Clinical Problem

The human gastrointestinal tract hosts trillions of microorganisms that is called “gut microbiota.” The gut microbiota is involved in a wide variety of physiological features and functions of the body. Thus, it is not surprising that any damage to the gut microbiota is associated with disorders in different body systems. Probiotics, defined as living microorganisms with health benefits for the host, can support or restore the composition of the gut microbiota. Numerous investigations have proved a relationship between the gut microbiota with normal brain function as well as many brain diseases, in which cognitive dysfunction is a common clinical problem. On the other hand, increasing evidence suggests that the existence of a healthy gut microbiota is crucial for normal cognitive processing. In this regard, interplay of the gut microbiota and cognition has been under focus of recent researches. In the present paper, I review findings of the studies considering beneficial effects of either gut microbiota or probiotic bacteria on the brain cognitive function in the healthy and disease statuses.

scholarly journals Zebrafish: A Promising Real-Time Model System for Nanotechnology-Mediated Neurospecific Drug Delivery

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Suraiya Saleem ◽  
Rajaretinam Rajesh Kannan
Keyword(s):  
Drug Delivery ◽  
Model System ◽  
Research Community ◽  
Therapeutic Interventions ◽  
Brain Diseases ◽  
Zebrafish Model ◽  
Time Model ◽  
High Fecundity ◽  
Novel Technologies ◽  
The Brain

AbstractDelivering drugs to the brain has always remained a challenge for the research community and physicians. The blood–brain barrier (BBB) acts as a major hurdle for delivering drugs to specific parts of the brain and the central nervous system. It is physiologically comprised of complex network of capillaries to protect the brain from any invasive agents or foreign particles. Therefore, there is an absolute need for understanding of the BBB for successful therapeutic interventions. Recent research indicates the strong emergence of zebrafish as a model for assessing the permeability of the BBB, which is highly conserved in its structure and function between the zebrafish and mammals. The zebrafish model system offers a plethora of advantages including easy maintenance, high fecundity and transparency of embryos and larvae. Therefore, it has the potential to be developed as a model for analysing and elucidating the permeability of BBB to novel permeation technologies with neurospecificity. Nanotechnology has now become a focus area within the industrial and research community for delivering drugs to the brain. Nanoparticles are being developed with increased efficiency and accuracy for overcoming the BBB and delivering neurospecific drugs to the brain. The zebrafish stands as an excellent model system to assess nanoparticle biocompatibility and toxicity. Hence, the zebrafish model is indispensable for the discovery or development of novel technologies for neurospecific drug delivery and potential therapies for brain diseases.

The Vegetative Status Correction in the Patients with Chronic Dyscirculatory Encephalopathy on the Sanatorium Rehabilitation Stage

10.12737/5760 ◽  
2014 ◽  
Vol 8 (1) ◽  
pp. 1-6
Author(s):  
Куликов ◽  
N. Kulikov ◽  
Череващенко ◽  
Lyubov Cherevashchenko ◽  
Череващенко ◽  
...  
Keyword(s):  
Laser Therapy ◽  
The State ◽  
The Body ◽  
Brain Diseases ◽  
Control Group ◽  
Autonomic Imbalance ◽  
Dyscirculatory Encephalopathy ◽  
Before And After ◽  
The Brain ◽  
Adaptive Reactions

Among vascular brain diseases a special place in its importance takes chronic cerebrovascular pathology in the form of dyscirculatory encephalopathy. The most frequently affected cerebral structures with discirculatory encephalopathy are those parts of the brain that are largely responsible for shaping over segmental vegetative disorders, which are characteristic of clinics chronic cerebrovascular insufficiency. The purpose of this work is to develop a new modern high technology of sanatorium rehabilitation of the patients with circulatory encephalopathy on stage I and to correct autonomic imbalance. The authors observed 60 patients who were divided into 2 groups. The control group received radon baths, the patients from the main group in addition to radon baths received laser therapy paravertebrally C1-Th3, according to scanning technique. In all patients before and after treatment the state of the autonomic nervous system studied. It was found that the initial manifestations of vascular encephalopathy accompanied by autonomic imbalance with a predominance of sympathetic tone, activation and inhibition effects of ergotrop activities segmental systems, primarily due to the parasympathetic division. The results of this study demonstrate feasibility of incorporating laser therapy in complex radon baths for rehabilitation of patients with circulatory encephalopathy autonomic imbalance. The findings suggest that improving the functional state mechanisms vegetative maintenance activities, which help to eliminate the state of surge and flow of adaptive reactions in the body.

scholarly journals Chitosan-Based Nanocarriers for Nose to Brain Delivery

2019 ◽  
Vol 9 (11) ◽  
pp. 2219 ◽  
Author(s):  
Blessing Atim Aderibigbe ◽  
Tobeka Naki
Keyword(s):  
Drug Delivery ◽  
Nasal Mucosa ◽  
Targeted Drug Delivery ◽  
Drug Uptake ◽  
Brain Diseases ◽  
In Vivo Studies ◽  
Brain Targeting ◽  
Prolonged Contact ◽  
Targeted Drug ◽  
The Brain

In the treatment of brain diseases, most potent drugs that have been developed exhibit poor therapeutic outcomes resulting from the inability of a therapeutic amount of the drug to reach the brain. These drugs do not exhibit targeted drug delivery mechanisms, resulting in a high concentration of the drugs in vital organs leading to drug toxicity. Chitosan (CS) is a natural-based polymer. It has unique properties such as good biodegradability, biocompatibility, mucoadhesive properties, and it has been approved for biomedical applications. It has been used to develop nanocarriers for brain targeting via intranasal administration. Nanocarriers such as nanoparticles, in situ gels, nanoemulsions, and liposomes have been developed. In vitro and in vivo studies revealed that these nanocarriers exhibited enhanced drug uptake to the brain with reduced side effects resulting from the prolonged contact time of the nanocarriers with the nasal mucosa, the surface charge of the nanocarriers, the nano size of the nanocarriers, and their capability to stretch the tight junctions within the nasal mucosa. The aforementioned unique properties make chitosan a potential material for the development of nanocarriers for targeted drug delivery to the brain. This review will focus on chitosan-based carriers for brain targeting.

scholarly journals Ocular in situ gel: An overview

2019 ◽  
Vol 9 (1) ◽  
pp. 337-347 ◽  
Author(s):  
Asmat Majeed ◽  
Nisar Ahmad Khan
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Ocular Drug Delivery ◽  
The Body ◽  
Drug Bioavailability ◽  
In Situ Gel ◽  
In Situ Gelling ◽  
Gel System

Eye is the most sensitive organ of the body. Designing of ocular drug delivery system is the  most challenging field for pharmaceutical scientists as less than 5% of administered drug enters the eye due to the complicated anatomical structure of the eye, small absorptive surface and low transparency of the cornea, lipophilicity of corneal epithelium, pre corneal loss (due to nasolacrimal drainage), bonding of the drug with proteins contained in tear fluid, blinking, low capacity of conjunctival sac, that restricts the entry of drug molecule at the site of action and ultimately leads to poor ocular therapy. To improve ophthalmic drug bioavailability, there are considerable efforts directed towards newer drug delivery systems for ophthalmic administration. These novel drug delivery systems offer manifold advantages over conventional systems as they increase the efficiency of drug delivery by improving the release profile and also reduce drug toxicity. A lot of research going on in this area proves the fact that in situ gelling systems can be beneficial in the ocular drug delivery. In situ gel forming systems are drug delivery systems that are in solution form before administration in the body but once administered, undergo  in situ gelation, to form a gel triggered by external stimulus such as temperature, pH etc.  This review is to Specify a brief summary about in situ gels, various approaches for in situ gelling systems, different types of polymers used in in situ gels, their mechanisms of gel formation and evaluation of polymeric in situ gel. Keywords: in situ gel, polymers, Temperature induced in situ gel system, pH induced in situ gel system, Ion activated systems.

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