scholarly journals Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1929 ◽  
Author(s):  
Salman Ul Islam ◽  
Adeeb Shehzad ◽  
Muhammad Bilal Ahmed ◽  
Young Sup Lee

Although the global prevalence of neurological disorders such as Parkinson’s disease, Alzheimer’s disease, glioblastoma, epilepsy, and multiple sclerosis is steadily increasing, effective delivery of drug molecules in therapeutic quantities to the central nervous system (CNS) is still lacking. The blood brain barrier (BBB) is the major obstacle for the entry of drugs into the brain, as it comprises a tight layer of endothelial cells surrounded by astrocyte foot processes that limit drugs’ entry. In recent times, intranasal drug delivery has emerged as a reliable method to bypass the BBB and treat neurological diseases. The intranasal route for drug delivery to the brain with both solution and particulate formulations has been demonstrated repeatedly in preclinical models, including in human trials. The key features determining the efficacy of drug delivery via the intranasal route include delivery to the olfactory area of the nares, a longer retention time at the nasal mucosal surface, enhanced penetration of the drugs through the nasal epithelia, and reduced drug metabolism in the nasal cavity. This review describes important neurological disorders, challenges in drug delivery to the disordered CNS, and new nasal delivery techniques designed to overcome these challenges and facilitate more efficient and targeted drug delivery. The potential for treatment possibilities with intranasal transfer of drugs will increase with the development of more effective formulations and delivery devices.

2020 ◽  
Vol 26 (11) ◽  
pp. 1128-1137 ◽  
Author(s):  
Mohammad A. Ansari ◽  
Ill-Min Chung ◽  
Govindasamy Rajakumar ◽  
Mohammad A. Alzohairy ◽  
Mohammad N. Alomary ◽  
...  

: Nanoparticles (NPs) are unique may be organic or inorganic, play a vital role in the development of drug delivery targeting the central nervous system (CNS). Intranasal drug delivery has shown to be an efficient strategy with attractive application for drug delivery to the CNS related diseases, such as Parkinson's disease, Alzheimer 's disease and brain solid tumors. Blood brain barrier (BBB) and blood-cerebrospinal fluid barriers are natural protective hindrances for entry of drug molecules into the CNS. Nanoparticles exhibit excellent intruding capacity for therapeutic agents and overcome protective barriers. By using nanotechnology based NPs targeted, drug delivery can be improved across BBB with discharge drugs in a controlled manner. NPs confer safe from degradation phenomenon. Several kinds of NPs are used for nose to the brain (N2B) enroute, such as lipidemic nanoparticles, polymeric nanoparticles, inorganic NPs, solid lipid NPs, dendrimers. Among them, popular lipidemic and polymeric NPs are discussed, and their participation in anti-cancer activity has also been highlighted in this review.


2021 ◽  
Vol 22 (12) ◽  
pp. 6442
Author(s):  
Aida Kouhi ◽  
Vyshnavi Pachipulusu ◽  
Talya Kapenstein ◽  
Peisheng Hu ◽  
Alan L. Epstein ◽  
...  

Due to their high specificity, monoclonal antibodies have been widely investigated for their application in drug delivery to the central nervous system (CNS) for the treatment of neurological diseases such as stroke, Alzheimer’s, and Parkinson’s disease. Research in the past few decades has revealed that one of the biggest challenges in the development of antibodies for drug delivery to the CNS is the presence of blood–brain barrier (BBB), which acts to restrict drug delivery and contributes to the limited uptake (0.1–0.2% of injected dose) of circulating antibodies into the brain. This article reviews the various methods currently used for antibody delivery to the CNS at the preclinical stage of development and the underlying mechanisms of BBB penetration. It also describes efforts to improve or modulate the physicochemical and biochemical properties of antibodies (e.g., charge, Fc receptor binding affinity, and target affinity), to adapt their pharmacokinetics (PK), and to influence their distribution and disposition into the brain. Finally, a distinction is made between approaches that seek to modify BBB permeability and those that use a physiological approach or antibody engineering to increase uptake in the CNS. Although there are currently inherent difficulties in developing safe and efficacious antibodies that will cross the BBB, the future prospects of brain-targeted delivery of antibody-based agents are believed to be excellent.


2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Massimo Masserini

The central nervous system, one of the most delicate microenvironments of the body, is protected by the blood-brain barrier (BBB) regulating its homeostasis. BBB is a highly complex structure that tightly regulates the movement of ions of a limited number of small molecules and of an even more restricted number of macromolecules from the blood to the brain, protecting it from injuries and diseases. However, the BBB also significantly precludes the delivery of drugs to the brain, thus, preventing the therapy of a number of neurological disorders. As a consequence, several strategies are currently being sought after to enhance the delivery of drugs across the BBB. Within this review, the recently born strategy of brain drug delivery based on the use of nanoparticles, multifunctional drug delivery systems with size in the order of one-billionth of meters, is described. The review also includes a brief description of the structural and physiological features of the barrier and of the most utilized nanoparticles for medical use. Finally, the potential neurotoxicity of nanoparticles is discussed, and future technological approaches are described. The strong efforts to allow the translation from preclinical to concrete clinical applications are worth the economic investments.


2020 ◽  
Vol 21 (14) ◽  
pp. 1136-1143 ◽  
Author(s):  
Javed Ahmad ◽  
Md. Rizwanullah ◽  
Saima Amin ◽  
Musarrat Husain Warsi ◽  
Mohammad Zaki Ahmad ◽  
...  

Background: Nanostructured lipid carriers (NLCs) are in high demand in the existing pharmaceutical domain due to its high versatility. It is the newer generation of lipid nanoparticulate systems having a solid matrix and greater stability at room temperature. Objective: To review the evidence related to the current state of the art of the NLCs system and its drug delivery perspectives to the brain. Methods: Scientific data search, review of the current state of the art and drug delivery perspectives to the brain for NLCs were undertaken to assess the applicability of NLCs in the management of neurological disorders through an intranasal route of drug administration Results: NLCs are designed to fulfill all the industrial needs like simple technology, low cost, scalability, and quantifications. Biodegradable and biocompatible lipids and surfactants used for NLCs have rendered them acceptable from regulatory perspectives as well. Apart from these, NLCs have unique properties of high drug payload, modulation of drug release profile, minimum drug expulsion during storage, and incorporation in various dosage forms like gel, creams, granules, pellets, powders for reconstitution and colloidal dispersion. Ease of surface- modification of NLCs enhances targeting efficiency and reduces systemic toxicity by providing site-specific delivery to the brain through the intranasal route of drug administration. Conclusion: The present review encompasses the in-depth discussion over the current state of the art of NLCs, nose-to-brain drug delivery perspectives, and its theranostic application as useful tools for better management of various neurological disorders. Further, pharmacokinetic consideration and toxicity concern is also discussed specifically for the NLCs system exploited in nose-to-brain delivery.


2021 ◽  
Vol 11 (3) ◽  
pp. 3640-3651

Neurological disorders are increasing worldwide due to the rapidly aging population, which increases healthcare costs. Drug delivery to the brain is challenging because of the brain's anatomy, and orally administered drugsare mostly unable to cross BBB. Intranasal (Nose to Brain) administration of drugs is one novel approach to address this challenge. Intranasal delivery has appeared to evade the blood-brain barrier (BBB) and deliver the drug into the CNS at a higher rate and degree than another traditional route. Transport of drugs from the nasal cavity to the brain along with olfactory and trigeminal nerves. The purpose of this review is drug delivery by the intranasal route for treating neurological disorders like Parkinson’s and depression because drug delivery by other routes is unable to cross BBB. Still, delivery through the intranasal route by using the nanotechnology approach is possible to deliver the drug directly to CNS.


2020 ◽  
Vol 26 (19) ◽  
pp. 2291-2305 ◽  
Author(s):  
Saurabh Mittal ◽  
Muhammad U. Ashhar ◽  
Farheen F. Qizilbash ◽  
Zufika Qamar ◽  
Jasjeet K. Narang ◽  
...  

Background: Human brain is amongst the most complex organs in human body, and delivery of therapeutic agents across the brain is a tedious task. Existence of blood brain barrier (BBB) protects the brain from invasion of undesirable substances; therefore it hinders the transport of various drugs used for the treatment of different neurological diseases including glioma, Parkinson's disease, Alzheimer's disease, etc. To surmount this barrier, various approaches have been used such as the use of carrier mediated drug delivery; use of intranasal route, to avoid first pass metabolism; and use of ligands (lactoferrin, apolipoprotein) to transport the drug across the BBB. Ligands bind with proteins present on the cell and facilitate the transport of drug across the cell membrane via. receptor mediated, transporter mediated or adsorptive mediated transcytosis. Objective: The main focus of this review article is to illustrate various studies performed using ligands for delivering drug across BBB; it also describes the procedure used by various researchers for conjugating the ligands to the formulation to achieve targeted action. Methods: Research articles that focused on the used of ligand conjugation for brain delivery and compared the outcome with unconjugated formulation were collected from various search engines like PubMed, Science Direct and Google Scholar, using keywords like ligands, neurological disorders, conjugation, etc. Results and Conclusion: Ligands have shown great potential in delivering drug across BBB for treatment of various diseases, yet extensive research is required so that the ligands can be used clinically for treating neurological diseases.


Author(s):  
V. KEERTHANA ◽  
S. DHANALAKSHMI ◽  
N. HARIKRISHNAN

Delivery of drugs into the brain is one of the most interesting and challenging areas of research. The blood-brain barrier (BBB) is a highly selective semipermeable membrane that separates blood from the brain in the central nervous system. It acts as a barrier to protect the brain from microbes, neurotoxins and other chemical substances and also blocks the entry of many drugs into the brain. An estimated 6.8 billion people die every year from CNS diseases like Parkinson’s disease, Alzheimer’s disease, sclerosis, brain stroke, dementia and others. According to WHO, one billion people are affected worldwide, about 50 million suffer from epilepsy and 24 million suffer from Alzheimer and other dementias. This indicates the importance of the delivery of drugs into the brain for treating various neurological diseases and psychological disorders. In drug targeting, a concept was introduced by Dr. Paul Ehrlich as a ‘magic bullet’ that gave tremendous hope for the researches to deliver drugs into the brain. This review discuses about various drug targeting strategies and applications of nanotechnology in designing drug delivery systems with the ability to cross through the BBB for treating neurological diseases.


2020 ◽  
Vol 21 (7) ◽  
pp. 628-646
Author(s):  
Gülcem Altinoglu ◽  
Terin Adali

Alzheimer’s disease (AD) is the most common neurodegenerative disease, and is part of a massive and growing health care burden that is destroying the cognitive function of more than 50 million individuals worldwide. Today, therapeutic options are limited to approaches with mild symptomatic benefits. The failure in developing effective drugs is attributed to, but not limited to the highly heterogeneous nature of AD with multiple underlying hypotheses and multifactorial pathology. In addition, targeted drug delivery to the central nervous system (CNS), for the diagnosis and therapy of neurological diseases like AD, is restricted by the challenges posed by blood-brain interfaces surrounding the CNS, limiting the bioavailability of therapeutics. Research done over the last decade has focused on developing new strategies to overcome these limitations and successfully deliver drugs to the CNS. Nanoparticles, that are capable of encapsulating drugs with sustained drug release profiles and adjustable physiochemical properties, can cross the protective barriers surrounding the CNS. Thus, nanotechnology offers new hope for AD treatment as a strong alternative to conventional drug delivery mechanisms. In this review, the potential application of nanoparticle based approaches in Alzheimer’s disease and their implications in therapy is discussed.


Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 566
Author(s):  
Jae-Geun Lee ◽  
Hyun-Ju Cho ◽  
Yun-Mi Jeong ◽  
Jeong-Soo Lee

The microbiota–gut–brain axis (MGBA) is a bidirectional signaling pathway mediating the interaction of the microbiota, the intestine, and the central nervous system. While the MGBA plays a pivotal role in normal development and physiology of the nervous and gastrointestinal system of the host, its dysfunction has been strongly implicated in neurological disorders, where intestinal dysbiosis and derived metabolites cause barrier permeability defects and elicit local inflammation of the gastrointestinal tract, concomitant with increased pro-inflammatory cytokines, mobilization and infiltration of immune cells into the brain, and the dysregulated activation of the vagus nerve, culminating in neuroinflammation and neuronal dysfunction of the brain and behavioral abnormalities. In this topical review, we summarize recent findings in human and animal models regarding the roles of the MGBA in physiological and neuropathological conditions, and discuss the molecular, genetic, and neurobehavioral characteristics of zebrafish as an animal model to study the MGBA. The exploitation of zebrafish as an amenable genetic model combined with in vivo imaging capabilities and gnotobiotic approaches at the whole organism level may reveal novel mechanistic insights into microbiota–gut–brain interactions, especially in the context of neurological disorders such as autism spectrum disorder and Alzheimer’s disease.


2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Roheela Yasmeen ◽  
Nida Mobeen ◽  
Muhammad Amjad Khan ◽  
Irfan Aslam ◽  
Samia Chaudhry

Epilepsy which is also called seizures disorder is an uncontrolled action of the central nervous system. Itis not a single disease but a set of neurological disorders. Actually in this situation, the brain does notreceive a precise signal and as a result an abnormal condition is produced that is usually involuntary inaction. In this review, we aimed to focus on the relationship of anti-epileptic drugs with sexual dysfunctionand adaptation of better remedies that improve a patient’s family life. Sexual dysfunction is a commoncomorbidity in people with epilepsy which badly affects their quality of life. Sexual dysfunction is causedby different factors like psychiatric problems, anti-epileptic drugs (AEDs) and social factors etc. Sexualdysfunctions include ejaculatory failure, lessen libido, penile erection in men and irregular menstrual cyclein women. Common drugs such as Topiramate, Gabapentin (GBP), Valproate (VA), Carbamazepine (CBZ),Olanzapine (OL) and Risperidone (RTG) that are in practice to treat epilepsy usually produced adverseeffect on sexual dysfunction. Even though a lot of studies have been carried out to control sexualdysfunction in epilepsy’s patient, but still research is going on. Medicine such as Cyproheptadine,Mianserin, Buspirone, Yohimbine were found better to treat epilepsy with minimum side effects of sexualdysfunction. Moreover, it is also seen that certain vasodilators, folate , and vitamin supplements areeffective in improving the quality of life.


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