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Pharmaceutics
Special Issues
Advances in Drug Delivery Systems for Targeted Neurological Therapies
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Advances in Drug Delivery Systems for Targeted Neurological Therapies

A Special Issue of Pharmaceutics (ISSN 1999-4923) belonging to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (30 September 2025) | Viewed by 6102

Editor

Dr. Shahrzad Latifi

E-Mail Website
Guest Editor
Department of Neuroscience, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV 26506, USA
Interests: stroke recovery; multiscale connectomics; brain immaging, neurotechnology; drug delivery for neurological diseases; artificial intelligence in brain and biological sciences
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The delivery of drugs to the central nervous system poses one of the greatest challenges in treating brain disorders. A major obstacle is the blood–brain barrier (BBB), which prevents drugs from crossing into the brain. Numerous clinical trials for various neurological disorders have failed over the past decades due to the inadequate concentration of drugs in the brain caused by this limitation. Novel brain targeting approaches are thus urgently required to overcome this barrier.

This Special Issue aims to provide a collection of new studies, robust reviews and innovative perspectives that could contribute to advancing drug delivery systems for targeted neurological therapies.

I look forward to receiving your contributions.

Dr. Shahrzad Latifi
Guest Editor

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 250 words) can be sent to the Editorial Office for assessment.

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-anonymized 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

  • drug delivery
  • brain
  • central nervous system
  • neurological disorders
  • blood–brain barrier
  • nanothechnology
  • nanotherapeutics
  • brain networks

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Published Papers (2 papers)

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Research

24 pages, 4478 KB  
Article
Citicoline Triggers Proteome Remodeling and Proteostatic Adaptation: Evidence from Shotgun Proteomics
by Dario Cavaterra, Sara Giammaria, Irene Pandino, Gabriele Antonio Zingale, Valerio Delli Paoli, Rebecca Fiore, Manuele Michelessi, Gloria Roberti, Carmela Carnevale, Lucia Tanga, Daniela Cazzato, Elisa Peroni, Giuseppe Grasso, Gianluca Manni, Alessio Bocedi, Francesco Oddone, Massimiliano Coletta, Diego Sbardella and Grazia Raffaella Tundo
Pharmaceutics 2026, 18(1), 61; https://doi.org/10.3390/pharmaceutics18010061 - 1 Jan 2026
Viewed by 1688
Abstract
Background/Objectives: Citicoline, also known as CDP-choline, is a nootropic agent currently used in the treatment of glaucoma and is undergoing evaluation as a first-line therapy in a multi-center, international, phase III, randomized clinical trial involving citicoline eyedrops (ClinicalTrials.gov ID: NCT05710198). Numerous clinical [...] Read more.
Background/Objectives: Citicoline, also known as CDP-choline, is a nootropic agent currently used in the treatment of glaucoma and is undergoing evaluation as a first-line therapy in a multi-center, international, phase III, randomized clinical trial involving citicoline eyedrops (ClinicalTrials.gov ID: NCT05710198). Numerous clinical and preclinical studies have linked the neuroenhancement and neuroprotective effects of citicoline to its role as a metabolic precursor for structural and functional components of cell membranes (such as phosphatidylcholine and sphingomyelin) and for neurotransmitters (e.g., acetylcholine and dopamine). However, compelling evidence suggests that the molecular mechanisms underlying its cytoprotective activity involve additional as-yet uncharacterized pharmacological actions. Methods: To further elucidate its pharmacology, we investigated the effect of two cytoprotective doses of citicoline (0.1 mM and 1 mM) on the global proteome of neuroblastoma cells using an unbiased shotgun proteomics approach. Results: With over 4000 unique proteins identified and quantified per experimental condition, the proteomics analysis revealed that citicoline, after 6 h of stimulation, induces a profound and robust remodeling of the intracellular proteome compared to untreated cells. Importantly, this effect was observed to significantly diminish by 18 h of stimulation, highlighting its transient nature (data are available via ProteomeXchange with identifier PXD061053). The clustering and rationalization of proteins upregulated by citicoline treatment identified the enrichment of key pathways for mRNA splicing, protein translation, proteostasis balance through the ubiquitin proteasome system (UPS), and mitochondrial metabolism. Conclusions: These proteomics findings introduce previously uncharacterized biological effects of citicoline and foster the working hypothesis that this drug may exert its cytoprotective activity through molecular mechanisms linked to the hormesis principle. These data further support the rationale for its clinical application in neurodegenerative processes and human disorders characterized by proteotoxicity. Full article
(This article belongs to the Special Issue Advances in Drug Delivery Systems for Targeted Neurological Therapies)
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15 pages, 2723 KB  
Article
Transdermal Delivery of Botulinum Neurotoxin A: A Novel Formulation with Therapeutic Potential
by Raj Kumar and Bal Ram Singh
Pharmaceutics 2025, 17(2), 146; https://doi.org/10.3390/pharmaceutics17020146 - 22 Jan 2025
Cited by 3 | Viewed by 3569
Abstract
Background: Botulinum neurotoxin is widely regarded as a “wonder medicine” due to its therapeutic efficacy in treating a variety of conditions. While it is traditionally classified as a neurotoxin, it is arguably more appropriate to refer to it as a neuromedicine. All FDA-approved [...] Read more.
Background: Botulinum neurotoxin is widely regarded as a “wonder medicine” due to its therapeutic efficacy in treating a variety of conditions. While it is traditionally classified as a neurotoxin, it is arguably more appropriate to refer to it as a neuromedicine. All FDA-approved formulations of botulinum neurotoxin are currently administered through intramuscular injections, with no other delivery methods widely used. The primary reasons for this include the following: (a) the extremely high potency of the toxin, (b) the potential for diffusion to adjacent muscles, (c) factors related to the site of administration (e.g., muscle thickness), (d) the large size of the molecule, (e) the impermeability of skin to large protein molecules, and (f) safety concerns. Despite these challenges, there is growing interest in the development of an effective transdermal formulation of botulinum neurotoxin. Refining and standardizing the delivery technology for topical or transdermal use remains an important goal for the future. Methods: The aim of this study was to develop a nanoemulsion-based transdermal formulation capable of delivering active botulinum neurotoxin (BoNT) through human skin. The goal was to demonstrate its efficacy in a mouse model, highlighting the therapeutic effects on both neuromuscular activity and hyperhidrosis. We successfully developed a nanoemulsion-based formulation that facilitates the transdermal delivery of BoNT. The formulation was homogeneous, stable, and efficacious. In a mouse model, we evaluated the neurotoxin’s impact on neuromuscular function using the Digital Abduction Score (DAS) for toe-spread and rota-rod assay to assess motor coordination. Results: The results confirmed the successful paralytic effect of the neuotoxin. The formulation significantly reduced sweating in the hyperhidrosis mouse model, indicating the therapeutic potential for this indication. Beyond the neurotoxin’s paralyzing effect, we also observed the recovery of nerve function, showing that the neurotoxin does not cause permanent damage, further underscoring its safety and efficacy. Conclusions: This formulation is the first of its kind to successfully deliver a large biomolecule like BoNT across the skin and produce a therapeutic effect. The ability to deliver large biomolecules transdermally has the potential to serve as a platform technology for treating a variety of conditions, including neuromuscular disorders, skin conditions, and localized pain management. Full article
(This article belongs to the Special Issue Advances in Drug Delivery Systems for Targeted Neurological Therapies)
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