AN UPDATED REVIEW ON THE APPLICATION OF DENDRIMERS AS SUCCESSFUL NANOCARRIERS FOR BRAIN DELIVERY OF THERAPEUTIC MOIETIES

It’s been nearly 100 y of effort to study the organization and role of the blood brain-barrier and still, we strive to find better techniques to overcome this barrier to deliver the drugs to the brain effectively with reduced systemic side effects. The advances in nanotechnology have given newer horizons in achieving this goal since the nano-scaled systems can modify an existing drug to have a high degree of sensitivity to the physiological conditions and specificity to reach the target organ. Among the various nanocarriers, dendrimers owing to their unique physical and chemical characteristics, represent a potential therapeutic tool in biomedical and pharmaceutical science. Dendrimers, an established polymeric nanocarrier system of the time, can deliver both drugs and genetic material and are being extensively studied to target the brain. The surface modification of dendrimers can reduce their innate toxicity problems and increase the therapeutic efficacy of brain disorders. This review article is an attempt to update on the potential of dendrimers explored in the past five years as a drug delivery avenue that can be considered as a promising solution in the management of a wide range of disorders affecting the central nervous system, including neoplastic, degenerative, and ischemic conditions. The following search criteria were used to expand the review article with the keywords dendrimers, novel drug delivery, nanoparticles, site-specific drug delivery etc.

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Nanotechnology Approaches for Enhanced CNS Drug Delivery in the Management of Schizophrenia

Advanced Pharmaceutical Bulletin ◽

10.34172/apb.2022.052 ◽

2021 ◽

Author(s):

Rajalakshmi R ◽

Krishnakumar N Menon ◽

Sreeja C Nair

Keyword(s):

Drug Delivery ◽

Targeted Drug Delivery ◽

Symptomatic Relief ◽

Therapeutic Strategies ◽

Review Article ◽

Visual Hallucinations ◽

Cns Drug Delivery ◽

The Central Nervous System ◽

The Brain

Schizophrenia is a neuropsychiatric disorder mainly affecting the central nervous system, presented with auditory and visual hallucinations, delusion and withdrawal from society. Abnormal dopamine levels mainly characterise the disease; various theories of neurotransmitters explain the pathophysiology of the disease. The current therapeutic approach deals with the systemic administration of drugs other than the enteral route, altering the neurotransmitter levels within the brain and providing symptomatic relief. Fluid biomarkers help in the early detection of the disease, which would improve the therapeutic efficacy. However, the major challenge faced in CNS drug delivery is the blood-brain barrier. Nanotherapeutic approaches may overcome these limitations, which will improve safety, efficacy, and targeted drug delivery. This review article addresses the main challenges faced in CNS drug delivery and the significance of current therapeutic strategies and nanotherapeutic approaches for a better understanding and enhanced drug delivery to the brain, which improve the quality of life of schizophrenia patients.

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Recent advancements in liposome-based strategies for effective drug delivery to the brain

Current Medicinal Chemistry ◽

10.2174/0929867328666201218121728 ◽

2020 ◽

Vol 28 ◽

Author(s):

Parvin Zaman ◽

Peter E. Penson ◽

George E. Barreto ◽

Amirhossein Sahebkar

Keyword(s):

Drug Delivery ◽

Targeted Drug Delivery ◽

Causes Of Death ◽

Biologically Active ◽

Large Molecules ◽

Wide Range ◽

Common Causes ◽

The Central Nervous System ◽

The Brain ◽

Active Substances

: Disorders of the central nervous system (CNS) and tumors of the brain are challenging to treat, and they rank amongst the most common causes of death worldwide. The delivery of drugs to the brain is problematic because the blood-brain barrier (BBB) effectively arrests the transport of large molecules (including drugs) from the blood to the CNS. Nanoparticle (NP)-mediated drug delivery has received much interest as a technique to overcome this difficulty. In particular, liposome NPs are promising candidates to carry and deliver drugs across the BBB and into the CNS. Liposomes are easy to prepare, highly biodegradable and biocompatible. Liposomes can be easily modified with various ligands to enable efficient and targeted drug delivery. Liposomes can promote increased cellular uptake of drugs and can reduce the extent to which efflux transporters can remove drugs. Liposomes can be loaded with a wide range of drugs and biologically active substances. In this review, we will summarize recent advances in research relating to liposome-based strategies to enable drug delivery across the BBB.

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Exosomes potential therapeutics

10.31219/osf.io/mhwt3 ◽

2021 ◽

Author(s):

Moataz Dowaidar

Keyword(s):

Drug Delivery ◽

Drug Efficacy ◽

Therapeutic Effects ◽

Drug Delivery Vehicles ◽

Molecular Features ◽

Transportation Capacity ◽

The Central Nervous System ◽

Novel Drug ◽

The Brain

Finding novel drug delivery techniques and enhancing current ones for better pharmacokinetics and enhanced transportation capacity through the central nervous system (CNS) is a key research topic. When proteins, nucleic acids and other macromolecules are used as CNS treatments, crossing the blood-brain barrier (BBB) is a challenge. Due to poor targeting, release of kinetics and failure to achieve brain therapeutic concentrations, the BBB restricts the predicted therapeutic effects on the CNS. As a result, following systemic administration, most potentially useful diagnostic and therapeutic medicines can not reach the brain. Many invasive procedures such as neurosurgery and BBB osmotic/biochemical opening are used to deliver medicine to the brain, suggesting a loss in drug efficacy and increased patient risks. Translating novel neurotherapeutics from the bench to the bedside will be hard unless we find a mechanism for delivering drugs that can successfully cross the BBB. Extracellular vesicles (EVs) or nanovesicles are now generally known to have a function in intercellular communication in both normal and pathological circumstances, including HIV infection. With EVs and HIV, researchers face many hurdles. Because of comparable structural and molecular features, investigations requiring separation of EVs and HIV may generate problems. currently investigating pathogenic pathways of viral protein-mediated neurotoxicity involving EVs. Furthermore, developing effective pharmacological amelioration strategies to counteract the harmful effects of HIV and eliminating HIV reservoirs is important, especially in people with HAND. As nanotechnology advances, many nanocarriers are being explored as a way of delivering medicines to the CNS. Exosomes show potential as drug delivery vehicles. Exosomes have an advantage in terms of potential because of their inherent ability to encapsulate biological and chemical compounds, the ease with which surface modification can be accomplished, and their endogenous nature. However, additional investigation is needed to overcome the challenges discovered in EV research before considering EVs as a feasible way of delivering medicines. Future investigations might focus on EV research concerns such as improved EV separation, loading, characterization, quantification, and in vivo tracking approaches.

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Management of Glioblastoma Multiforme by Phytochemicals: Applications of Nanoparticle Based Targeted Drug Delivery System

Current Drug Targets ◽

10.2174/1389450121666200727115454 ◽

2020 ◽

Vol 21 ◽

Author(s):

Sayed Md Mumtaz ◽

Gautam Bhardwaj ◽

Shikha Goswami ◽

Rajiv Kumar Tonk ◽

Ramesh K. Goyal ◽

...

Keyword(s):

Drug Delivery ◽

Glioblastoma Multiforme ◽

Drug Delivery System ◽

Delivery System ◽

Genetic Disorder ◽

Drug Regimen ◽

Brain Regions ◽

Radio Therapy ◽

Novel Drug ◽

The Brain

: The Glioblastoma Multiforme (GBM; grade IV astrocytoma) exhort tumor of star-shaped glial cell in the brain. It is a fast-growing tumor that spreads to nearby brain regions specifically to cerebral hemispheres in frontal and temporal lobes. The etiology of GBM is unknown, but major risk factors are genetic disorder like neurofibromatosis and schwanomatosis which develop the tumor in the nervous system. The management of GBM with chemo-radio therapy leads to resistance and current drug regimen like Temozolomide (TMZ) is less efficacious. The reasons behind failure of drugs are due to DNA alkylation in cell cycle by enzyme DNA guanidase and mitochondrial dysfunction. Naturally occurring bio-active compounds from plants known as phytochemicals, serve as vital sources for anti-cancer drugs. Some typical examples include taxol analogs, vinca alkaloids such as vincristine, vinblastine, podophyllotoxin analogs, camptothecin, curcumin, aloe emodin, quercetin, berberine e.t.c. These phytochemicals often act via regulating molecular pathways which are implicated in growth and progression of cancers. However the challenges posed by the presence of BBB/BBTB to restrict passage of these phytochemicals, culminates in their low bioavailability and relative toxicity. In this review we integrated nanotech as novel drug delivery system to deliver phytochemicals from traditional medicine to the specific site within the brain for the management of GBM.

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Polymer-Drug Conjugates as Nanotheranostic Agents

Journal of Nanotheranostics ◽

10.3390/jnt2010005 ◽

2021 ◽

Vol 2 (1) ◽

pp. 63-81

Author(s):

Sajana Manandhar ◽

Erica Sjöholm ◽

Johan Bobacka ◽

Jessica M. Rosenholm ◽

Kuldeep K. Bansal

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Treatment Options ◽

The Body ◽

Drug Conjugates ◽

Imaging Characteristics ◽

Wide Range ◽

Systemic Side Effects ◽

Theranostic Agents ◽

The Stability

Since the last decade, the polymer-drug conjugate (PDC) approach has emerged as one of the most promising drug-delivery technologies owing to several benefits like circumventing premature drug release, offering controlled and targeted drug delivery, improving the stability, safety, and kinetics of conjugated drugs, and so forth. In recent years, PDC technology has advanced with the objective to further enhance the treatment outcomes by integrating nanotechnology and multifunctional characteristics into these systems. One such development is the ability of PDCs to act as theranostic agents, permitting simultaneous diagnosis and treatment options. Theranostic nanocarriers offer the opportunity to track the distribution of PDCs within the body and help to localize the diseased site. This characteristic is of particular interest, especially among those therapeutic approaches where external stimuli are supposed to be applied for abrupt drug release at the target site for localized delivery to avoid systemic side effects (e.g., Visudyne®). Thus, with the help of this review article, we are presenting the most recent updates in the domain of PDCs as nanotheranostic agents. Different methodologies utilized to design PDCs along with imaging characteristics and their applicability in a wide range of diseases, have been summarized in this article.

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Stem Cells as a Target for the Delivery of Active Molecules to Skin by Topical Administration

International Journal of Molecular Sciences ◽

10.3390/ijms21062251 ◽

2020 ◽

Vol 21 (6) ◽

pp. 2251

Author(s):

Hamid-Reza Ahmadi-Ashtiani ◽

Parisa Bishe ◽

Anna Baldisserotto ◽

Piergiacomo Buso ◽

Stefano Manfredini ◽

...

Keyword(s):

Drug Delivery ◽

Stem Cells ◽

Topical Administration ◽

Therapeutic Interventions ◽

Skin Cancers ◽

Basic And Applied Research ◽

Hair Follicle Growth ◽

Novel Drug ◽

Physical And Chemical ◽

Cell Gene

Cutaneous stem cells, gained great attention in the field of regenerative medicine as a potential therapeutic target for the treatment of skin and hair disorders and various types of skin cancers. Cutaneous stem cells play a key role in several processes like the renovation of skin structures in the condition of homeostasis and after injuries, the hair follicle growth and the reconstruction and production of melanocytes. Thus, gaining effective access to skin stem cells for therapeutic interventions that often involve active molecules with non-favorable characteristics for skin absorption is a valuable achievement. The topical route with high patient compliance and several other benefits is gaining increasing importance in basic and applied research. However, the major obstacle for topical drug delivery is the effective barrier provided by skin against penetration of the vast majority of exogenous molecules. The research in this field is focusing more and more on new strategies to circumvent and pass this barrier effectively. In this article the existing approaches are discussed considering physical and chemical methods along with utilization of novel drug delivery systems to enhance penetration of drugs to the skin. In particular, attention has been paid to studies finalized to the delivery of molecules to cutaneous stem cells with the aim of transferring signals, modulating their metabolic program, inducing physiological modifications and stem cell gene therapy.

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

Molecules ◽

10.3390/molecules25081929 ◽

2020 ◽

Vol 25 (8) ◽

pp. 1929 ◽

Cited By ~ 6

Author(s):

Salman Ul Islam ◽

Adeeb Shehzad ◽

Muhammad Bilal Ahmed ◽

Young Sup Lee

Keyword(s):

Drug Delivery ◽

Neurological Disorders ◽

Neurological Diseases ◽

Nasal Delivery ◽

Intranasal Route ◽

Drug Molecules ◽

Surface Enhanced ◽

Effective Delivery ◽

The Central Nervous System ◽

The Brain

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.

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UNDERSTANDING NOVEL POLYMER AND LIPID BASED CARRIER SYSTEMS IN CLINICIAN PERSPECTIVE

International Journal of Medical Science and Diagnosis Research ◽

10.32553/ijmsdr.v4i10.685 ◽

2020 ◽

Vol 4 (10) ◽

Author(s):

Kallem Sharat Venkat Reddy

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Drug Dosage ◽

Delivery Systems ◽

Review Article ◽

Point Of View ◽

Smart Polymers ◽

The Past ◽

Novel Drug ◽

Carrier Systems

From the past two decades, technological advancements in science and chemistry made possible many new drug delivery systems that have the potential to completely change the course of routine therapeutic ways. Lipid and polymer-based drug delivery systems are considered to be the pillars of many drug dosage forms, irrespective of their route of administration. With increasing knowledge on their chemistry, lipids and polymers are being modified and used as potential novel drug delivery systems with smart polymers and lipid nanotechnology paving the way for efficient drug delivery into the patient. This review article covers the swing of these drug delivery systems in the current market and interpreting all this from a health care professional’s point of view. Keywords: Gene delivery, Lipid based drug delivery, Polymer based drug delivery, Target specific drugs, Solid lipid nanoparticles

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Modern aspects of neuropathogenesis and neurological manifestations of COVID-19

INTERNATIONAL NEUROLOGICAL JOURNAL ◽

10.22141/2224-0713.17.2.2021.229887 ◽

2021 ◽

Vol 17 (2) ◽

pp. 6-15

Author(s):

L.A. Dziak ◽

O.S. Tsurkalenko ◽

K.V. Chekha ◽

V.M. Suk

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Psychiatric Symptoms ◽

Clinical Manifestations ◽

The Body ◽

Altered Level ◽

Wide Range ◽

The Central Nervous System ◽

The Brain

Coronavirus infection is a systemic pathology resulting in impairment of the nervous system. The involvement of the central nervous system in COVID-19 is diverse by clinical manifestations and main mechanisms. The mechanisms of interrelations between SARS-CoV-2 and the nervous system include a direct virus-induced lesion of the central nervous system, inflammatory-mediated impairment, thrombus burden, and impairment caused by hypoxia and homeostasis. Due to the multi-factor mechanisms (viral, immune, hypoxic, hypercoagulation), the SARS-CoV-2 infection can cause a wide range of neurological disorders involving both the central and peripheral nervous system and end organs. Dizziness, headache, altered level of consciousness, acute cerebrovascular diseases, hypogeusia, hyposmia, peripheral neuropathies, sleep disorders, delirium, neuralgia, myalgia are the most common signs. The structural and functional changes in various organs and systems and many neurological symptoms are determined to persist after COVID-19. Regardless of the numerous clinical reports about the neurological and psychiatric symptoms of COVID-19 as before it is difficult to determine if they are associated with the direct or indirect impact of viral infection or they are secondary to hypoxia, sepsis, cytokine reaction, and multiple organ failure. Penetrated the brain, COVID-19 can impact the other organs and systems and the body in general. Given the mechanisms of impairment, the survivors after COVID-19 with the infection penetrated the brain are more susceptible to more serious diseases such as Parkinson’s disease, cognitive decline, multiple sclerosis, and other autoimmune diseases. Given the multi-factor pathogenesis of COVID-19 resulting in long-term persistence of the clinical symptoms due to impaired neuroplasticity and neurogenesis followed by cholinergic deficiency, the usage of Neuroxon® 1000 mg a day with twice-day dosing for 30 days. Also, a long-term follow-up and control over the COVID-19 patients are recommended for the prophylaxis, timely determination, and correction of long-term complications.

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