scholarly journals Allogenic Fc Domain-Facilitated Uptake of IgG in Nasal Lamina Propria: Friend or Foe for Intranasal CNS Delivery?

Pharmaceutics ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 107 ◽  
Author(s):  
Simone Ladel ◽  
Johannes Flamm ◽  
Arghavan Soleimani Zadeh ◽  
Dorothea Filzwieser ◽  
Julia-Christina Walter ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Lamina Propria ◽  
Messenger Rna ◽  
Ex Vivo ◽  
Neurological Diseases ◽  
Olfactory Mucosa ◽  
Basal Cells ◽  
Delivery Methods ◽  
Lymphoid Follicles ◽  
Brain Drug Delivery

Background: The use of therapeutic antibodies for the treatment of neurological diseases is of increasing interest. Nose-to-brain drug delivery is one strategy to bypass the blood brain barrier. The neonatal Fc receptor (FcRn) plays an important role in transepithelial transcytosis of immunoglobulin G (IgG). Recently, the presence of the FcRn was observed in nasal respiratory mucosa. The aim of the present study was to determine the presence of functional FcRn in olfactory mucosa and to evaluate its role in drug delivery. Methods: Immunoreactivity and messenger RNA (mRNA) expression of FcRn was determined in ex vivo porcine olfactory mucosa. Uptake of IgG was performed in a side-by-side cell and analysed by immunofluorescence. Results: FcRn was found in epithelial and basal cells of the olfactory epithelium as well as in glands, cavernous bodies and blood vessels. Allogenic porcine IgGs were found time-dependently in the lamina propria and along axonal bundles, while only small amounts of xenogenic human IgGs were detected. Interestingly, lymphoid follicles were spared from allogenic IgGs. Conclusion: Fc-mediated transport of IgG across the nasal epithelial barrier may have significant potential for intranasal delivery, but the relevance of immune interaction in lymphoid follicles must be clarified to avoid immunogenicity.

scholarly journals Nanoemulsions for “Nose-to-Brain” Drug Delivery

Pharmaceutics ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 84 ◽  
Author(s):  
Maria Bonferoni ◽  
Silvia Rossi ◽  
Giuseppina Sandri ◽  
Franca Ferrari ◽  
Elisabetta Gavini ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Neurological Diseases ◽  
High Surface ◽  
High Surface Area ◽  
Brain Targeting ◽  
Nasal Administration ◽  
Toxic Substances ◽  
Onset Of Action ◽  
Brain Drug Delivery ◽  
The Brain

The blood–brain barrier (BBB) plays a fundamental role in protecting the brain from toxic substances and therefore also controls and restricts the entry of therapeutic agents. The nasal administration of drugs using the nose-to-brain pathway allows direct drug targeting into the brain, avoiding the first-pass effect and bypassing the BBB. Through the nasal route, the drug can access the brain directly along the trigeminal and olfactory nerves, which are located in the upper part of the nasal cavity. Nanoemulsions are formulations belonging to the field of nanomedicine. They consist of emulsions (commonly oil in water) stabilized by one or more surfactants—and eventually co-surfactants—delivered in droplets of small dimensions (sizes of 100–300 nm or less) with a high surface area. A mucoadhesive polymer such as chitosan can be added to the formulation to impair rapid nasal clearance. Nanoemulsions represent promising formulations to deliver drugs directly into the brain through the intranasal route. Therefore, they can be used as a possible alternative to oral administration, avoiding problems such as low solubility in water, poor bioavailability, enzymatic degradation and slow onset of action. This review focuses the present situation in literature regarding the use of nanoemulsions for nose-to-brain targeting, with particular attention to recent publications. Nasal nanoemulsions appear to be effective, non-invasive and safe drug delivery systems to achieve brain targeting for the treatment of neurological diseases.

Immunohistochemical Analysis of the Olfactory Mucosa by Use of Antibodies to Brain Proteins and Cytokeratin

1989 ◽  
Vol 98 (5) ◽  
pp. 384-388 ◽  
Author(s):  
Masuo Yamagishi ◽  
Satoshi Hasegawa ◽  
Yuichi Nakano ◽  
Sugata Takahashi ◽  
Toshihiko Iwanaga
Keyword(s):  
Lamina Propria ◽  
Neuron Specific Enolase ◽  
Immunohistochemical Analysis ◽  
Olfactory Mucosa ◽  
Basal Cells ◽  
Neurofilament Protein ◽  
Receptor Cells ◽  
Nerve Bundles ◽  
Protein Immunoreactivity ◽  
Cerebellar Purkinje Cells

The present study deals with the immunohistochemical detection of four brain-derived proteins and cytokeratin in the normal olfactory mucosa of humans and guinea pigs. Neurofilament protein immunoreactivity was found in the olfactory vesicles, dendrites, and perikaryon of receptor cells, and in thick nerve bundles located deep in the lamina propria. The antiserum to neuron-specific enolase (NSE) selectively stained olfactory receptor cells throughout the length of the bundles. The NSE immunoreactivity also was recognized in nerve bundles of various sizes throughout the lamina propria. Glia-specific S-100 protein immunoreactivity was present in Bowman's glands as well as in all nerve bundles in the lamina propria, but not in any cellular elements constituting the olfactory epithelium. Immunoreactivity for spot-35 protein, which was considered to be specific for cerebellar Purkinje cells, was found in flasklike cells (microvillar cells) occurring near the free surface of the epithelium. The basal cells in the olfactory and respiratory epithelium were stained positively with a cytokeratin antiserum.

scholarly journals Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier

2014 ◽  
Vol 2014 ◽  
pp. 1-37 ◽  
Author(s):  
Ravi Kant Upadhyay
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Neurological Diseases ◽  
Drug Carriers ◽  
Delivery Systems ◽  
Delivery Methods ◽  
Deep Tissue ◽  
Therapeutic Alternatives ◽  
Pharmaceutical Agents ◽  
Chimeric Peptides

Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods.

scholarly journals The Olfactory Mucosa of the Sheep

1970 ◽  
Vol 23 (2) ◽  
pp. 447 ◽  
Author(s):  
Jean E Kratzing
Keyword(s):  
Electron Microscopy ◽  
Lamina Propria ◽  
Light And Electron Microscopy ◽  
Free Edge ◽  
Cell Types ◽  
Olfactory Nerve ◽  
Olfactory Mucosa ◽  
Basal Cells ◽  
Supporting Cells ◽  
Receptor Cells

The olfactory mucosa of the sheep was studied by light and electron microscopy. The epithelium conforms to the general vertebrate pattern and consists of olfactory receptor cells, supporting, and basal cells. The free edge of the epithelium is made up of long microvilli from the supporting cells and olfactory rods of the receptor cells, each carrying 40-50 cilia. All cell types contain large dark granules which may be the site of olfactory pigment. The basement membrane is not visible in light microscopy and is fine and discontinuous in electron microscopy. Bowman's glands are simple, tubular, mucus-secreting glands in the lamina propria. Their cells contain basal granules resembling those in the epithelial cells. The lamina propria also contains bundles of fine, unmyelinated, olfactory nerve fibres which are the proximal continuations of the receptor cells.

Blood–Brain Barrier Opening and Drug Delivery Using Focused Ultrasound and Microbubbles

2013 ◽  
pp. 148-159
Author(s):  
Elisa E. Konofagou
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Neurological Diseases ◽  
Brain Barrier ◽  
Limiting Factor ◽  
Delivery Problem ◽  
Brain Drug Delivery ◽  
Blood Brain ◽  
The Brain

Current treatments of neurological and neurodegenerative diseases are limited due to the lack of a truly non-invasive, transient, and regionally selective brain drug delivery method. The brain is particularly difficult to deliver drugs to because of the blood-brain barrier (BBB). The impermeability of the BBB is due to the tight junctions connecting adjacent endothelial cells and highly regulatory transport systems of the endothelial cell membranes. The main function of the BBB is ion and volume regulation to ensure conditions necessary for proper synaptic and axonal signaling. However, the same permeability properties that keep the brain healthy also constitute the cause of the tremendous obstacles posed in its pharmacological treatment. The BBB prevents most neurologically active drugs from entering the brain and, as a result, has been isolated as the rate-limiting factor in brain drug delivery. Until a solution to the trans-BBB delivery problem is found, treatments of neurological diseases will remain impeded. Over the past decade, methods that combine Focused Ultrasound (FUS) and microbubbles have been shown to offer the unique capability of noninvasively, locally and transiently opening the BBB so as to treat central nervous system (CNS) diseases. Four of the main challenges that lie ahead are to: 1) assess its safety profile, 2) unveil the mechanism by which the BBB opens and closes, 3) control and predict the opened BBB properties and duration of the opening and 4) assess its premise in brain drug delivery. All these challenges will be discussed, findings in both small (mice) and large (non-human primates) animals will be shown and finally the case for this technique for clinical applications will be made.

Recent Advances in Novasome Formulation Technology

2014 ◽  
Vol 7 (2) ◽  
pp. 2407-2411
Author(s):  
J M Shah ◽  
N.H Shah ◽  
Hadiya P D
Keyword(s):  
Drug Delivery ◽  
Effective Means ◽  
Entrapment Efficiency ◽  
Bilayer Membrane ◽  
Water Soluble ◽  
Delivery Methods ◽  
Liposomal Drug ◽  
Pharmaceutical Technology ◽  
Insoluble Drugs ◽  
Novel Drug

Pharmaceutical technology has developed various newer modes of novel drug delivery aspects. Modifications in the previously existing drug delivery methods have led to various newly innovated technologies serving as a safe and effective means of improvement over the existing ones. Novasome technology is one of the new innovations of liposomes which have solved many of the problems related to liposomal drug delivery system. It offers a seven bilayer membrane which has the ability to incorporate both water soluble and insoluble drugs. It has an excellent entrapment efficiency which provides better medication. Formulation of novasomes is achieved in a high shear device. Due to its numerous advantages, novasomes have been used extensively in various fields like cosmetics, chemical, personal care, foods, pharmaceuticals and agrochemicals.

Nose-to-Brain Drug Delivery by Nanoparticles in the Treatment of Neurological Disorders

2014 ◽  
Vol 21 (37) ◽  
pp. 4247-4256 ◽  
Author(s):  
Wei-Yi Ong ◽  
Suku-Maran Shalini ◽  
Luca Costantino
Keyword(s):  
Drug Delivery ◽  
Neurological Disorders ◽  
Brain Drug Delivery

Brain Drug Delivery: Overcoming the Blood-brain Barrier to Treat Tauopathies

2020 ◽  
Vol 26 (13) ◽  
pp. 1448-1465 ◽  
Author(s):  
Jozef Hanes ◽  
Eva Dobakova ◽  
Petra Majerova
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Neurodegenerative Disorders ◽  
Brain Barrier ◽  
Neuronal Function ◽  
Brain Drug Delivery ◽  
Naturally Occurring ◽  
Blood Brain ◽  
Traditional Approaches ◽  
The Brain

Tauopathies are neurodegenerative disorders characterized by the deposition of abnormal tau protein in the brain. The application of potentially effective therapeutics for their successful treatment is hampered by the presence of a naturally occurring brain protection layer called the blood-brain barrier (BBB). BBB represents one of the biggest challenges in the development of therapeutics for central nervous system (CNS) disorders, where sufficient BBB penetration is inevitable. BBB is a heavily restricting barrier regulating the movement of molecules, ions, and cells between the blood and the CNS to secure proper neuronal function and protect the CNS from dangerous substances and processes. Yet, these natural functions possessed by BBB represent a great hurdle for brain drug delivery. This review is concentrated on summarizing the available methods and approaches for effective therapeutics’ delivery through the BBB to treat neurodegenerative disorders with a focus on tauopathies. It describes the traditional approaches but also new nanotechnology strategies emerging with advanced medical techniques. Their limitations and benefits are discussed.

Polymeric Nanoparticles for Brain Drug Delivery - A Review

2020 ◽  
Vol 21 (9) ◽  
pp. 649-660
Author(s):  
Subashini Raman ◽  
Syed Mahmood ◽  
Ayah R. Hilles ◽  
Md Noushad Javed ◽  
Motia Azmana ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Surface Modification ◽  
Polymeric Nanoparticles ◽  
Drug Loading ◽  
Preparation Methods ◽  
Brain Drug Delivery ◽  
Polymeric Nanoparticle ◽  
Relationship Of ◽  
The Relationship ◽  
The Brain

Background: Blood-brain barrier (BBB) plays a most hindering role in drug delivery to the brain. Recent research comes out with the nanoparticles approach, is continuously working towards improving the delivery to the brain. Currently, polymeric nanoparticle is extensively involved in many therapies for spatial and temporal targeted areas delivery. Methods: We did a non-systematic review, and the literature was searched in Google, Science Direct and PubMed. An overview is provided for the formulation of polymeric nanoparticles using different methods, effect of surface modification on the nanoparticle properties with types of polymeric nanoparticles and preparation methods. An account of different nanomedicine employed with therapeutic agent to cross the BBB alone with biodistribution of the drugs. Results: We found that various types of polymeric nanoparticle systems are available and they prosper in delivering the therapeutic amount of the drug to the targeted area. The effect of physicochemical properties on nanoformulation includes change in their size, shape, elasticity, surface charge and hydrophobicity. Surface modification of polymers or nanocarriers is also vital in the formulation of nanoparticles to enhance targeting efficiency to the brain. Conclusion: More standardized methods for the preparation of nanoparticles and to assess the relationship of surface modification on drug delivery. While the preparation and its output like drug loading, particle size, and charge, permeation is always conflicted, so it requires more attention for the acceptance of nanoparticles for brain delivery.

Sign in / Sign up

Export Citation Format

Share Document