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Pharmaceutics
Special Issues
Advances in Drug Targeting for Central Nervous System Disease
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Advances in Drug Targeting for Central Nervous System Disease

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 11461

Special Issue Editors

Dr. Ivana Cacciatore

E-Mail Website
Guest Editor
Dipartimento di Farmacia, Università degli Studi “G. D'Annunzio”, Via dei Vestini 31, 66100 Chieti, Italy
Interests: Alzheimer's disease; Parkinson's disease; antimicrobials; synthesis of peptides
Special Issues, Collections and Topics in MDPI journals
Dr. Anna Wiktorowska-Owczarek

E-Mail Website
Guest Editor
Department of Pharmacology and Toxicology, Medical University of Lodz, 7/9 Zeligowskiego, 90-752 Lodz, Poland
Interests: endoplasmic reticulum stress; inflammation; NSAIDs; antidepressants; antioxidants; pharmacology
Dr. Sokołowska Paulina

E-Mail Website
Guest Editor
Department of Pharmacology and Toxicology, Medical University of Lodz, 7/9 Zeligowskiego, 90-752 Lodz, Poland
Interests: neuroprotection; neurotoxicology; nanoparticles; nanomedicine; drug development; cell signaling

Special Issue Information

Dear Colleagues,

Central nervous system (CNS) diseases such as psychiatric and neurological are a major challenge for medicine and public health worldwide. Currently available drugs offer temporary relief from the symptoms of the neurodegenerative disorder, but they do not arrest or reverse the disease. Adverse effects and resistance to traditional therapies require looking for new options. CNS diseases are multifaceted disorders with diverse and not fully understood pathophysiological mechanisms, e.g., the development of inflammatory processes, oxidative and endoplasmic reticulum stress, disturbance of neuronal-glial communication. The pathological processes are associated with specific signaling pathways, and their elements can become strategic points for development of new drugs and for new applications of already approved.

This Special Issue of Pharmaceutics titled “Advances in Drug Targeting for Central Nervous System Diseases”, will gather discoveries of new drug targets, drug formation and targeted delivery with emphasis on strategies that may alter signaling pathways involved in pathological processes of CNS diseases to stop their progress or even prevent them. Research papers and Reviews on drugs already approved and new molecules are welcome.

We are looking forward for your contribution.

Dr. Ivana Cacciatore
Dr. Anna Wiktorowska-Owczarek
Dr. Sokołowska Paulina
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • CNS diseases
  • disturbance of neuronal-glial communication
  • drug targeting
  • drug formation
  • targeted drug delivery
  • endoplasmic reticulum stress
  • neurodegeneration
  • neuroinflammation
  • neuroplasticity
  • neuroprotection
  • neurotransmitters
  • neurotrophins
  • oxidative stress
  • signaling pathways

Published Papers (5 papers)

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Research

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16 pages, 2938 KiB  
Article
What Are the Key Anatomical Features for the Success of Nose-to-Brain Delivery? A Study of Powder Deposition in 3D-Printed Nasal Casts
by Clément Rigaut, Laura Deruyver, Maxime Niesen, Marc Vander Ghinst, Jonathan Goole, Pierre Lambert and Benoit Haut
Pharmaceutics 2023, 15(12), 2661; https://doi.org/10.3390/pharmaceutics15122661 - 23 Nov 2023
Cited by 1 | Viewed by 984
Abstract
Nose-to-brain delivery is a promising way to improve the treatment of central nervous system disorders, as it allows the bypassing of the blood–brain barrier. However, it is still largely unknown how the anatomy of the nose can influence the treatment outcome. In this [...] Read more.
Nose-to-brain delivery is a promising way to improve the treatment of central nervous system disorders, as it allows the bypassing of the blood–brain barrier. However, it is still largely unknown how the anatomy of the nose can influence the treatment outcome. In this work, we used 3D printing to produce nasal replicas based on 11 different CT scans presenting various anatomical features. Then, for each anatomy and using the Design of Experiments methodology, we characterised the amount of a powder deposited in the olfactory region of the replica as a function of multiple parameters (choice of the nostril, device, orientation angle, and the presence or not of a concomitant inspiration flow). We found that, for each anatomy, the maximum amount of powder that can be deposited in the olfactory region is directly proportional to the total area of this region. More precisely, the results show that, whatever the instillation strategy, if the total area of the olfactory region is below 1500 mm2, no more than 25% of an instilled powder can reach this region. On the other hand, if the total area of the olfactory region is above 3000 mm2, the deposition efficiency reaches 50% with the optimal choice of parameters, whatever the other anatomical characteristics of the nasal cavity. Finally, if the relative difference between the areas of the two sides of the internal nasal valve is larger than 20%, it becomes important to carefully choose the side of instillation. This work, by predicting the amount of powder reaching the olfactory region, provides a tool to evaluate the adequacy of nose-to-brain treatment for a given patient. While the conclusions should be confirmed via in vivo studies, it is a first step towards personalised treatment of neurological pathologies. Full article
(This article belongs to the Special Issue Advances in Drug Targeting for Central Nervous System Disease)
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21 pages, 2097 KiB  
Article
Dietary Polyphenols Decrease Chemokine Release by Human Primary Astrocytes Responding to Pro-Inflammatory Cytokines
by Mikolaj Grabarczyk, Dominika Ksiazek-Winiarek, Andrzej Glabinski and Piotr Szpakowski
Pharmaceutics 2023, 15(9), 2294; https://doi.org/10.3390/pharmaceutics15092294 - 07 Sep 2023
Viewed by 909
Abstract
Astrocytes are considered to be the dominant cell fraction of the central nervous system. They play a supportive and protective role towards neurons, and regulate inflammatory processes; they thus make suitable targets for drugs and supplements, such as polyphenolic compounds. However, due to [...] Read more.
Astrocytes are considered to be the dominant cell fraction of the central nervous system. They play a supportive and protective role towards neurons, and regulate inflammatory processes; they thus make suitable targets for drugs and supplements, such as polyphenolic compounds. However, due to their wide range, knowledge of their anti-inflammatory potential remains relatively incomplete. The aim of this study was therefore to determine whether myricetin and chrysin are able to decrease chemokine release in reactive astrocytes. To assess the antioxidant and anti-inflammatory potential of polyphenols, human primary astrocytes were cultured in the presence of a reactive and neurotoxic astrocyte-inducing cytokine mixture (TNF-α, IL-1a, C1q), either alone or in the presence of myricetin or chrysin. The examined polyphenols were able to modify the secretion of chemokines by human cortical astrocytes, especially CCL5 (chrysin), CCL1 (myricetin) and CCL2 (both), while cell viability was not affected. Surprisingly, the compounds did not demonstrate any antioxidant properties in the astrocyte cultures. Full article
(This article belongs to the Special Issue Advances in Drug Targeting for Central Nervous System Disease)
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Review

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45 pages, 1441 KiB  
Review
Inhibition of Protein Aggregation and Endoplasmic Reticulum Stress as a Targeted Therapy for α-Synucleinopathy
by Natalia Siwecka, Kamil Saramowicz, Grzegorz Galita, Wioletta Rozpędek-Kamińska and Ireneusz Majsterek
Pharmaceutics 2023, 15(8), 2051; https://doi.org/10.3390/pharmaceutics15082051 - 30 Jul 2023
Cited by 1 | Viewed by 1875
Abstract
α-synuclein (α-syn) is an intrinsically disordered protein abundant in the central nervous system. Physiologically, the protein regulates vesicle trafficking and neurotransmitter release in the presynaptic terminals. Pathologies related to misfolding and aggregation of α-syn are referred to as α-synucleinopathies, and they constitute a [...] Read more.
α-synuclein (α-syn) is an intrinsically disordered protein abundant in the central nervous system. Physiologically, the protein regulates vesicle trafficking and neurotransmitter release in the presynaptic terminals. Pathologies related to misfolding and aggregation of α-syn are referred to as α-synucleinopathies, and they constitute a frequent cause of neurodegeneration. The most common α-synucleinopathy, Parkinson’s disease (PD), is caused by abnormal accumulation of α-syn in the dopaminergic neurons of the midbrain. This results in protein overload, activation of endoplasmic reticulum (ER) stress, and, ultimately, neural cell apoptosis and neurodegeneration. To date, the available treatment options for PD are only symptomatic and rely on dopamine replacement therapy or palliative surgery. As the prevalence of PD has skyrocketed in recent years, there is a pending issue for development of new disease-modifying strategies. These include anti-aggregative agents that target α-syn directly (gene therapy, small molecules and immunization), indirectly (modulators of ER stress, oxidative stress and clearance pathways) or combine both actions (natural compounds). Herein, we provide an overview on the characteristic features of the structure and pathogenic mechanisms of α-syn that could be targeted with novel molecular-based therapies. Full article
(This article belongs to the Special Issue Advances in Drug Targeting for Central Nervous System Disease)
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16 pages, 2519 KiB  
Review
The Potential of the Nose-to-Brain Delivery of PACAP for the Treatment of Neuronal Disease
by Asma Cherait, William A. Banks and David Vaudry
Pharmaceutics 2023, 15(8), 2032; https://doi.org/10.3390/pharmaceutics15082032 - 28 Jul 2023
Cited by 1 | Viewed by 2109
Abstract
Research on the neuroprotective effect of pituitary adenylate cyclase-activating polypeptide (PACAP) and its use as a therapeutic agent has grown over the past 30 years. Both in vitro and in vivo experiments have shown that PACAP exerts a strong neuroprotective effect in many [...] Read more.
Research on the neuroprotective effect of pituitary adenylate cyclase-activating polypeptide (PACAP) and its use as a therapeutic agent has grown over the past 30 years. Both in vitro and in vivo experiments have shown that PACAP exerts a strong neuroprotective effect in many central and peripheral neuronal diseases. Various delivery routes have been employed from intravenous (IV) injections to intracerebroventricular (ICV) administration, leading either to systemic or topical delivery of the peptide. Over the last decade, a growing interest in the use of intranasal (IN) administration of PACAP and other therapeutic agents has emerged as an alternative delivery route to target the brain. The aim of this review is to summarize the findings on the neuroprotective effect of PACAP and to discuss how the IN administration of PACAP could contribute to target the effects of this pleiotropic peptide. Full article
(This article belongs to the Special Issue Advances in Drug Targeting for Central Nervous System Disease)
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24 pages, 1015 KiB  
Review
Current Treatments and New, Tentative Therapies for Parkinson’s Disease
by Teresa Pardo-Moreno, Victoria García-Morales, Sami Suleiman-Martos, Antonio Rivas-Domínguez, Himan Mohamed-Mohamed, Juan José Ramos-Rodríguez, Lucía Melguizo-Rodríguez and Anabel González-Acedo
Pharmaceutics 2023, 15(3), 770; https://doi.org/10.3390/pharmaceutics15030770 - 25 Feb 2023
Cited by 7 | Viewed by 4581
Abstract
Parkinson’s disease (PD) is a neurodegenerative pathology, the origin of which is associated with the death of neuronal cells involved in the production of dopamine. The prevalence of PD has increased exponentially. The aim of this review was to describe the novel treatments [...] Read more.
Parkinson’s disease (PD) is a neurodegenerative pathology, the origin of which is associated with the death of neuronal cells involved in the production of dopamine. The prevalence of PD has increased exponentially. The aim of this review was to describe the novel treatments for PD that are currently under investigation and study and the possible therapeutic targets. The pathophysiology of this disease is based on the formation of alpha-synuclein folds that generate Lewy bodies, which are cytotoxic and reduce dopamine levels. Most pharmacological treatments for PD target alpha-synuclein to reduce the symptoms. These include treatments aimed at reducing the accumulation of alpha-synuclein (epigallocatechin), reducing its clearance via immunotherapy, inhibiting LRRK2, and upregulating cerebrosidase (ambroxol). Parkinson’s disease continues to be a pathology of unknown origin that generates a significant social cost for the patients who suffer from it. Although there is still no definitive cure for this disease at present, there are numerous treatments available aimed at reducing the symptomatology of PD in addition to other therapeutic alternatives that are still under investigation. However, the therapeutic approach to this pathology should include a combination of pharmacological and non-pharmacological strategies to maximise outcomes and improve symptomatological control in these patients. It is therefore necessary to delve deeper into the pathophysiology of the disease in order to improve these treatments and therefore the quality of life of the patients. Full article
(This article belongs to the Special Issue Advances in Drug Targeting for Central Nervous System Disease)
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