scholarly journals Targeting Systems to the Brain Obtained by Merging Prodrugs, Nanoparticles, and Nasal Administration

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1144
Author(s):  
Giada Botti ◽  
Alessandro Dalpiaz ◽  
Barbara Pavan
Keyword(s):  
Blood Brain Barrier ◽  
Brain Targeting ◽  
Nasal Administration ◽  
Efflux Transporter ◽  
Active Efflux ◽  
Valuable Alternative ◽  
Hydrophilic Drugs ◽  
Neuroactive Drugs ◽  
The Brain ◽  
Nanoparticulate Systems

About 40 years ago the lipidization of hydrophilic drugs was proposed to induce their brain targeting by transforming them into lipophilic prodrugs. Unfortunately, lipidization often transforms a hydrophilic neuroactive agent into an active efflux transporter (AET) substrate, with consequent rejection from the brain after permeation across the blood brain barrier (BBB). Currently, the prodrug approach has greatly evolved in comparison to lipidization. This review describes the evolution of the prodrug approach for brain targeting considering the design of prodrugs as active influx substrates or molecules able to inhibit or elude AETs. Moreover, the prodrug approach appears strategic in optimization of the encapsulation of neuroactive drugs in nanoparticulate systems that can be designed to induce their receptor-mediated transport (RMT) across the BBB by appropriate decorations on their surface. Nasal administration is described as a valuable alternative to obtain the brain targeting of drugs, evidencing that the prodrug approach can allow the optimization of micro or nanoparticulate nasal formulations of neuroactive agents in order to obtain this goal. Furthermore, nasal administration is also proposed for prodrugs characterized by peripheral instability but potentially able to induce their targeting inside cells of the brain.

Liposomes: Novel Drug Delivery Approach for Targeting Parkinson’s Disease

2020 ◽  
Vol 26 (37) ◽  
pp. 4721-4737 ◽  
Author(s):  
Bhumika Kumar ◽  
Mukesh Pandey ◽  
Faheem H. Pottoo ◽  
Faizana Fayaz ◽  
Anjali Sharma ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Targeting ◽  
Neural Cells ◽  
Blood Brain ◽  
The Brain

Parkinson’s disease is one of the most severe progressive neurodegenerative disorders, having a mortifying effect on the health of millions of people around the globe. The neural cells producing dopamine in the substantia nigra of the brain die out. This leads to symptoms like hypokinesia, rigidity, bradykinesia, and rest tremor. Parkinsonism cannot be cured, but the symptoms can be reduced with the intervention of medicinal drugs, surgical treatments, and physical therapies. Delivering drugs to the brain for treating Parkinson’s disease is very challenging. The blood-brain barrier acts as a highly selective semi-permeable barrier, which refrains the drug from reaching the brain. Conventional drug delivery systems used for Parkinson’s disease do not readily cross the blood barrier and further lead to several side-effects. Recent advancements in drug delivery technologies have facilitated drug delivery to the brain without flooding the bloodstream and by directly targeting the neurons. In the era of Nanotherapeutics, liposomes are an efficient drug delivery option for brain targeting. Liposomes facilitate the passage of drugs across the blood-brain barrier, enhances the efficacy of the drugs, and minimize the side effects related to it. The review aims at providing a broad updated view of the liposomes, which can be used for targeting Parkinson’s disease.

scholarly journals Intranasal Nanoemulsions for Direct Nose-to-Brain Delivery of Actives for CNS Disorders

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1230
Author(s):  
Shiv Bahadur ◽  
Dinesh M. Pardhi ◽  
Jarkko Rautio ◽  
Jessica M. Rosenholm ◽  
Kamla Pathak
Keyword(s):  
Rapid Development ◽  
Brain Targeting ◽  
Nasal Administration ◽  
Future Research ◽  
Brain Delivery ◽  
Olfactory Pathway ◽  
Nasal Drug Delivery ◽  
Cns Diseases ◽  
Biodistribution Studies ◽  
The Brain

The treatment of various central nervous system (CNS) diseases has been challenging, despite the rapid development of several novel treatment approaches. The blood–brain barrier (BBB) is one of the major issues in the treatment of CNS diseases, having major role in the protection of the brain but simultaneously constituting the main limiting hurdle for drugs targeting the brain. Nasal drug delivery has gained significant interest for brain targeting over the past decades, wherein the drug is directly delivered to the brain by the trigeminal and olfactory pathway. Various novel and promising formulation approaches have been explored for drug targeting to the brain by nasal administration. Nanoemulsions have the potential to avoid problems, including low solubility, poor bioavailability, slow onset of action, and enzymatic degradation. The present review highlights research scenarios of nanoemulsions for nose-to-brain delivery for the management of CNS ailments classified on the basis of brain disorders and further identifies the areas that remain unexplored. The significance of the total dose delivered to the target region, biodistribution studies, and long-term toxicity studies have been identified as the key areas of future research.

Drug Delivery Systems and Strategies to Overcome the Barriers of Brain

2021 ◽  
Vol 28 ◽  
Author(s):  
Yogesh Garg ◽  
Deepak N Kapoor ◽  
Abhishek Kumar Sharma ◽  
Amit Bhatia
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Brain Barrier ◽  
Olfactory Pathway ◽  
Hydrophilic Drugs ◽  
Blood Brain ◽  
Effective Delivery ◽  
The Brain

Abstract: The transport of drugs to the central nervous system is the most challenging task for conventional drug delivery systems. Reduced permeability of drugs through the blood-brain barrier is a major hurdle in delivering drugs to the brain. Hence, various strategies for improving drug delivery through the blood-brain barrier are currently being explored. Novel drug delivery systems (NDDS) offer several advantages, including high chemical and biological stability, suitability for both hydrophobic and hydrophilic drugs, and can be administered through different routes. Furthermore, the conjugation of suitable ligands with these carriers tend to potentiate targeting to the endothelium of the brain and could facilitate the internalization of drugs through endocytosis. Further, the intranasal route has also shown potential, as a promising alternate route, for the delivery of drugs to the brain. This can deliver the drugs directly to the brain through the olfactory pathway. In recent years, several advancements have been made to target and overcome the barriers of the brain. This article deals with a detailed overview of the diverse strategies and delivery systems to overcome the barriers of the brain for effective delivery of drugs.

scholarly journals ApoE-Targeting Increases the Transfer of Solid Lipid Nanoparticles with Donepezil Cargo across a Culture Model of the Blood–Brain Barrier

Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 38
Author(s):  
Gizem Rüya Topal ◽  
Mária Mészáros ◽  
Gergő Porkoláb ◽  
Anikó Szecskó ◽  
Tamás Ferenc Polgár ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Solid Lipid Nanoparticles ◽  
Lipid Nanoparticles ◽  
Brain Barrier ◽  
Brain Targeting ◽  
Solid Lipid ◽  
Blood Brain ◽  
Culture Model ◽  
The Brain

Pharmacological treatment of central nervous system (CNS) disorders is difficult, because the blood–brain barrier (BBB) restricts the penetration of many drugs into the brain. To solve this unmet therapeutic need, nanosized drug carriers are the focus of research efforts to develop drug delivery systems for the CNS. For the successful delivery of nanoparticles (NPs) to the brain, targeting ligands on their surface is necessary. Our research aim was to design a nanoscale drug delivery system for a more efficient transfer of donepezil, an anticholinergic drug in the therapy of Alzheimer’s disease across the BBB. Rhodamine B-labeled solid lipid nanoparticles with donepezil cargo were prepared and targeted with apolipoprotein E (ApoE), a ligand of BBB receptors. Nanoparticles were characterized by measurement of size, polydispersity index, zeta potential, thermal analysis, Fourier-transform infrared spectroscopy, in vitro release, and stability. Cytotoxicity of nanoparticles were investigated by metabolic assay and impedance-based cell analysis. ApoE-targeting increased the uptake of lipid nanoparticles in cultured brain endothelial cells and neurons. Furthermore, the permeability of ApoE-targeted nanoparticles across a co-culture model of the BBB was also elevated. Our data indicate that ApoE, which binds BBB receptors, can potentially be exploited for successful CNS targeting of solid lipid nanoparticles.

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.

scholarly journals Brain Targeting Through Intranasal Route: An Overview

2021 ◽  
pp. 112-124
Author(s):  
Sorakayala Venkata Anusha ◽  
Jonnala Ratna ◽  
Srirama Swarnalatha ◽  
Maruvajala Vidyavathi
Keyword(s):  
Drug Delivery ◽  
Small Molecules ◽  
Local Treatment ◽  
Systemic Circulation ◽  
Brain Targeting ◽  
Nasal Administration ◽  
Toxic Substances ◽  
Large Molecules ◽  
Nasal Route ◽  
The Brain

Brain targeting has always been challenging due to the presence of physiological barriers by Changing the integrity of these barriers, so as to allow the toxic substances, bacteria and viruses into the brain, Which may severely damage the central nervous system .This problem can be reduced by delivering drugs through the intra nasal route, which by passes the blood brain barrier and reaches into the brain. Nasal route is a non-invasive type, widely used for the local treatment as well as used for systemic therapy as drug delivery directly goes in to systemic circulation. Nasal route provides good absorption of small molecules compared to that of large molecules, absorption of small molecules and large molecules can be increased by absorption promoters. Different drug delivery devices are developed for nasal administration like liquids, semi-solid and solid formulation are consider to deliver the drugs to treat most of  the CNS diseases (i.e. Parkinson’s, Alzheimer’s disease) because it requires specific targeting of drugs to the brain. This review highlighted the challenges, approaches for brain targeting and various drug delivery systems developed with different drugs targeting to brain through nasal administration.

scholarly journals Niosome: A Promising Nanocarrier for Natural Drug Delivery through Blood-Brain Barrier

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Mahmoud Gharbavi ◽  
Jafar Amani ◽  
Hamidreza Kheiri-Manjili ◽  
Hossein Danafar ◽  
Ali Sharafi
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Targeting ◽  
Routes Of Administration ◽  
Packing Factor ◽  
Blood Brain ◽  
Natural Drugs ◽  
Pharmaceutical Uses ◽  
The Brain

Niosomes (the nonionic surfactant vesicles), considered as novel drug delivery systems, can improve the solubility and stability of natural pharmaceutical molecules. They are established to provide targeting and controlled release of natural pharmaceutical compounds. Many factors can influence on niosome construction such as the preparation method, type and amount of surfactant, drug entrapment, temperature of lipids hydration, and the packing factor. The present review discusses about the most important features of niosomes such as their diverse structures, the different preparation approaches, characterization techniques, factors that affect their stability, their use by various routes of administration, their therapeutic applications in comparison with natural drugs, and specially the brain targeting with niosomes-ligand conjugation. It also provides recent data about the various types of ligand agents which make available active targeting drug delivery to the central neuron system. This system has an optimistic upcoming in pharmaceutical uses, mostly with the improving availability of innovative schemes to overcome blood-brain barrier and targeting the niosomes to the brain.

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