Nanoparticles as Drug Delivery Systems for the Brain

2005 ◽  
pp. 714-731
2021 ◽  
Vol 18 ◽  
Author(s):  
Panoraia I. Siafaka ◽  
Gökce Mutlu ◽  
Neslihan Üstündağ Okur

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.


2020 ◽  
Vol 26 (31) ◽  
pp. 3871-3883
Author(s):  
Ece Ö. Bülbül ◽  
Ioannis D. Karantas ◽  
Mehmet E. Okur ◽  
Panoraia I. Siafaka ◽  
Neslihan Ü. Okur

Background: Schizophrenia belongs to mental illnesses affecting 1% of the worldwide population. Its therapy is still unmet; thus, researchers aimed to develop new pharmacological molecules which can improve its management. Methods: Moreover, the current typical and atypical antipsychotics should be formulated in more efficacious systems that can deliver the drug in the brain with as few side effects as possible. Further, the development of long-acting efficient drug delivery systems could be significant in minimizing frequent dosing which is nonpreferred to schizophrenics. Results: Herein, authors focused on current developments of antipsychotic medications used in schizophrenia management. Various studies, which include the use of first and second-generation antipsychotics, were analyzed according to their efficacy. In fact, in this review, oral, injectable, transdermal and intranasal formulations entrapped antipsychotics are presented to be valuable guidance for scientists to formulate more effective drug delivery systems for schizophrenic patients. Conclusions: This review aimed to assist researchers working on schizophrenia management by summarizing current medications and newly synthesized drug delivery systems recently found in the literature.


2021 ◽  
Vol 28 ◽  
Author(s):  
Yogesh Garg ◽  
Deepak N Kapoor ◽  
Abhishek Kumar Sharma ◽  
Amit Bhatia

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.


2020 ◽  
Vol 26 (12) ◽  
pp. 1331-1344
Author(s):  
Shiv Bahadur ◽  
Nidhi Sachan ◽  
Ranjit K. Harwansh ◽  
Rohitas Deshmukh

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.


Author(s):  
Viana Manrique-Suárez ◽  
Nelson Santiago Vispo ◽  
Oliberto Sánchez Ramos

: The main obstacle to biopharmaceutical delivery in therapeutic concentration into the brain for treating neurological disorders is the presence of the blood-brain barrier (BBB). The physiological process of receptor-mediated transcytosis (RMT) to transport cargo through the brain endothelial cells toward brain parenchyma has prompted researchers to search for non-natural ligands that can be used to transport drugs across the BBB. Conjugation of drugs to RMT ligands would be an effective strategy for its delivery to the central nervous system. An attractive approach to identify novel transcytosing ligands is the screening by phage display combinatorial libraries. The main technology strength lies in the large variety of exogenous peptides or proteins displayed on the phage's surface. Here, we provide a mini-review of phage display technology using in vitro and in vivo BBB models for the development of peptide-mediated drug delivery systems.


2020 ◽  
Vol 20 (30) ◽  
pp. 2777-2788
Author(s):  
Bhumika Kumar ◽  
Mukesh Pandey ◽  
Faizana Fayaz ◽  
Tareq Abu Izneid ◽  
Faheem Hyder Pottoo ◽  
...  

Parkinson’s disease (PD) is one of the most prevalent and severe neurodegenerative disease affecting more than 6.1 million people globally. It is characterized by age-related progressive deterioration of neurological functions caused by neuronal damage or neuronal death. During PD, the dopamineproducing cells in the substantia nigra region of the brain degenerate, which leads to symptoms like resting tremors and rigidity. Treatment of PD is very challenging due to the blood-brain barrier, which restricts the drug from reaching the brain. Conventional drug delivery systems possess a limited capacity to cross the blood barrier, leading to low bioavailability and high toxicity (due to off-site drug release). Therefore, it becomes necessary to accelerate the development of novel drug delivery systems, including nanoparticles, microemulsions, matrix systems, solid dispersions, liposomes, and solid lipid nanoparticles for the treatment of PD. Exosomes are biological lipid bilayer membrane vesicles produced by nearly all mammalian cells. The characteristics of vesicles are unique to their cell of origin and are primarily involved in intracellular communication. Exosomes, due to their nanoscale size, could easily permeate across the central nervous system, which makes them ideal for targeting the neurons in the substantia nigra. Exosomes could be efficient drug carrier systems for brain targeting, which can increase the efficacy of the drug and minimize the side effects. The review aims at providing a broad updated view of exosomes and their application in the treatment of PD.


2020 ◽  
Vol 26 (27) ◽  
pp. 3281-3299
Author(s):  
Deepshi Arora ◽  
Shailendra Bhatt ◽  
Manish Kumar ◽  
Hari D.C. Vattikonda ◽  
Yugam Taneja ◽  
...  

Background: Alzheimer is the primary cause of death in the various countries that affects wide strata of the population. The treatment of it is restricted to a few conventional oral medications that act only superficially. It is evident that the delivery of a drug to the brain across the blood-brain barrier is challenging as the BBB is armed with several efflux transporters like the P-glycoprotein as well as nasal mucociliary clearance adds up leading to decreased concentration and reduced therapeutic efficacy. Considering these, the intranasal IN route of drug administration is emerging as an alternative route for systemic delivery of a drug to the brain. The intranasal (IN) administration of lipid nanoparticles loaded with cerebroactive drugs showed promise in treating various neurodegenerative diseases, since the nasal route allows the direct nose to brain delivery by means of solid lipid nanoparticles (SLN’s). The tailoring of intranasal lipid particulate drug delivery systems is a pleasing approach to facilitate uptake of therapeutic agents at the desired site of action, particularly when a free drug has poor pharmacokinetics/ biodistribution (PK/BD) or significant off-site toxicities. Objectives: 1) In this review, key challenges and physiological mechanisms regulating intranasal brain delivery in Alzheimer’s disease, ex vivo studies, pharmacokinetics parameters including brain uptake and histopathological studies are thoroughly discussed. : 2) A thorough understanding of the in vivo behaviour of the intranasal drug carriers will be the elusive goal. : 3) The article emphasizes to drag the attention of the research community working in the intranasal field towards the challenges and hurdles of the practical applicability of intranasal delivery of cerebroactive drugs. Method: Various electronic databases, journals like nanotechnology and nanoscience, dove press are reviewed for the collection and compilation of data. Results: From in vivo biodistribution studies, pharmacokinetics parameters, and gamma scintigraphy images of various drugs, it is speculated that intranasal lipid particulates drug delivery system shows better brain targeting efficiency for various CNS disorders in comparison to other routes. Conclusion: Various routes are explored for the delivery of drugs to increase bioavailability in the brain for CNS disorders but the intranasal route shows better results that pave the way for success in the future if properly explored.


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