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Pharmaceuticals
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Drug Delivery across the Blood–Brain Barrier
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Drug Delivery across the Blood–Brain Barrier

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmaceutical Technology".

Deadline for manuscript submissions: closed (25 February 2025) | Viewed by 4207

Special Issue Editor

Dr. Touraj Ehtezazi

E-Mail Website
Guest Editor
Reader In Pharmaceutics, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK
Interests: fast-dissolving oral films; three-dimensional printing; fused deposition modelling; inkjet method; nanofibers; liposomes; natural products
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Brain diseases, disorders, and injuries involve damage to the neurons, with devastating outcomes and a considerable societal and economic impact of over USD 1.06tn. Brain diseases include multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, motor neuron disease, ischemic stroke, haemorrhagic stroke, and cancer. Several medicines and interventions have been developed for the treatment of brain diseases, improving the clinical outcomes. However, we are far from the desired therapeutic targets. Brain remyelination and resolving brain inflammation are unmet needs which require researcher’s attention. Although multiple investigations have been conducted in this field, due to complex nature of brain diseases, brain physiology, and anatomy, progress is slow. Therefore, further research on drug delivery to the brain is needed, and drug delivery systems must be optimised on a continuous basis.

This Special Issue will delve into novel drug delivery systems for the treatment of brain diseases, disorders, and injuries, including those that cross the blood–brain barrier and deliver cargo. Novel approaches for the treatment of neuroinflammation and remyelination will also be presented.

The following approaches will also be considered:

  • Nose-to-brain drug delivery;
  • Pharmaceutical approaches to normalising blood–brain barrier function;
  • Use of nanoparticles and ICV injections for drug delivery to the brain;
  • Employing magnetically guided nanoparticles as drug carriers;
  • The use of biomimetic nanoparticles to target inflammation in the brain;
  • The use of peptide-based self-assembled nanoparticles;
  • Employing solid lipid nanoparticles for the delivery of siRNA to brain neurons;
  • Nanoparticles to promote remyelination in the brain;
  • Nanoparticles for the treatment of traumatic brain injury.

Dr. Touraj Ehtezazi
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 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. Pharmaceuticals 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

  • blood–brain barrier
  • drug delivery
  • brain diseases
  • neuroinflammation
  • remyelination

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Published Papers (3 papers)

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11 pages, 952 KiB  
Article
A Classification-Based Blood–Brain Barrier Model: A Comparative Approach
by Ralph Saber and Sandy Rihana
Pharmaceuticals 2025, 18(6), 773; https://doi.org/10.3390/ph18060773 - 22 May 2025
Viewed by 438
Abstract
Background and Objectives: Drug permeability across the blood–brain barrier (BBB) remains a significant challenge in drug discovery, prompting extensive efforts to develop in silico predictive models. Most existing models rely on molecular descriptors to characterize drug properties. Feature selection algorithms play a [...] Read more.
Background and Objectives: Drug permeability across the blood–brain barrier (BBB) remains a significant challenge in drug discovery, prompting extensive efforts to develop in silico predictive models. Most existing models rely on molecular descriptors to characterize drug properties. Feature selection algorithms play a crucial role in identifying the most relevant descriptors, thereby enhancing prediction accuracy. Methods: In this study, we compare the effectiveness of sequential feature selection (SFS) and genetic algorithms (GAs) in optimizing descriptor selection for BBB permeability prediction. Five different classifiers were initially trained on a dataset using eight molecular descriptors. Each classifier was then retrained using the descriptors selected by SFS and GA separately. Results: The results indicate that the GA method outperformed SFS, leading to a higher prediction accuracy (96.23%) when combined with a support vector machine (SVM) classifier. Furthermore, the GA approach, utilizing a fitness function based on classifier performance, consistently improved prediction accuracy across all tested models, whereas SFS showed lower effectiveness. Additionally, this study highlights the critical role of polar surface area in determining drug permeability across the BBB. Conclusions: These findings suggest that genetic algorithms provide a more robust approach than sequential feature selection for identifying key molecular descriptors in BBB permeability prediction. Full article
(This article belongs to the Special Issue Drug Delivery across the Blood–Brain Barrier)
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25 pages, 13480 KiB  
Article
Comparison of Drug Delivery Systems with Different Types of Nanoparticles in Terms of Cellular Uptake and Responses in Human Endothelial Cells, Pericytes, and Astrocytes
by Hakan Sahin, Oguz Yucel, Paul Holloway, Eren Yildirim, Serkan Emik, Gulten Gurdag, Gamze Tanriverdi and Gozde Erkanli Senturk
Pharmaceuticals 2024, 17(12), 1567; https://doi.org/10.3390/ph17121567 - 22 Nov 2024
Cited by 2 | Viewed by 1686
Abstract
Background/Objectives: The key components of the blood–brain barrier (BBB) are endothelial cells, pericytes, astrocytes, and the capillary basement membrane. The BBB serves as the main barrier for drug delivery to the brain and is the most restrictive endothelial barrier in the body. [...] Read more.
Background/Objectives: The key components of the blood–brain barrier (BBB) are endothelial cells, pericytes, astrocytes, and the capillary basement membrane. The BBB serves as the main barrier for drug delivery to the brain and is the most restrictive endothelial barrier in the body. Nearly all large therapeutic molecules and over 90% of small-molecule drugs cannot cross the BBB. To overcome this challenge, nanotechnology, particularly drug delivery systems such as nanoparticles (NPs), have gained significant attention. Methods: Poly(lactide-co-glycolide) (PLGA) and albumin-based NPs (bovine/human), with or without transferrin (Tf) ligands (BSA, HSA, BSA-Tf, HSA-Tf), and nanolipid carriers (NLC) were synthesized. The interactions of these NPs with human brain microvascular endothelial cells (hBMECs), human brain vascular pericytes (hBVPs), and human astrocytes (hASTROs) were analyzed. Results: At doses of 15.62 µg/mL, 31.25 µg/mL, and 62.5 µg/mL, none of the NPs caused toxic effects on hBMECs, hBVPs, or hASTROs after 3 h of incubation. All NPs were internalized by the cells, but BSA-Tf and HSA-Tf showed significantly higher uptake in hBMECs in a dose-dependent manner. Ultrastructural analysis revealed notable differences between NP formulation and cell type. Conclusions: Our findings underscore the potential of ligand-targeted NPs to selectively interact with BBB endothelial cells. Ultrastructural analysis reveals distinct cellular processing pathways for various NP formulations across BBB-associated cell types, with autophagy emerging as a crucial mechanism for NP handling in pericytes and astrocytes. Changes in NP chemical properties upon biological exposure present significant challenges for nanomedicine design, emphasizing the need for further investigation into NP interactions at the cellular and subcellular levels. Full article
(This article belongs to the Special Issue Drug Delivery across the Blood–Brain Barrier)
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11 pages, 226 KiB  
Case Report
Intranasal Human-Recombinant Nerve Growth Factor Enhances Motor and Cognitive Function Recovery in a Child with Severe Traumatic Brain Injury
by Lorenzo Di Sarno, Lavinia Capossela, Serena Ferretti, Luigi Manni, Marzia Soligo, Susanna Staccioli, Eleonora Napoli, Riccardo Burattini, Antonio Gatto and Antonio Chiaretti
Pharmaceuticals 2025, 18(2), 163; https://doi.org/10.3390/ph18020163 - 25 Jan 2025
Cited by 1 | Viewed by 1361
Abstract
Introduction: Traumatic brain injury (TBI) in pediatric population is responsible for significant mortality and morbidity, particularly among children aged 0–4 and young adults aged 15–24. The developing brain’s unique characteristics may increase vulnerability to injuries, potentially leading to long-term cognitive and motor [...] Read more.
Introduction: Traumatic brain injury (TBI) in pediatric population is responsible for significant mortality and morbidity, particularly among children aged 0–4 and young adults aged 15–24. The developing brain’s unique characteristics may increase vulnerability to injuries, potentially leading to long-term cognitive and motor deficits. Current therapeutic options for neuronal regeneration post-TBI are limited, although neurotrophins, especially nerve growth factor (NGF), show promise in enhancing recovery. NGF can mitigate excitotoxicity and promote neuroprotection, particularly by intranasal administration, which is attractive because of its non-invasive nature. Case Presentation: A three-year-old boy suffered from severe TBI due to a car accident, leading to multiple complications, including a basilar skull fracture and cerebral venous sinus thrombosis. Initial assessments revealed significant neurological impairments. After intensive care and rehabilitation, the child exhibited gradual improvements in consciousness and motor functions but continued to face challenges, particularly with left-sided hemiparesis. Nine months post-injury, he began intranasal administration of human-recombinant NGF (hr-NGF) as part of a clinical trial. Discussion: Following hr-NGF treatment, the child demonstrated notable advancements in motor function, achieving independent standing and walking. Cognitive assessments indicated improvements in various domains, including verbal comprehension and executive functioning. EEG results showed reduced epileptiform activity. These findings suggest that hr-NGF may facilitate recovery in pediatric TBI cases by enhancing both motor and cognitive outcomes. Conclusions: This case highlights the potential role of intranasal hr-NGF administration as a therapeutic strategy for improving neurological recovery in children with severe TBI. The positive clinical outcomes support further exploration of NGF as a viable treatment option to mitigate long-term sequelae associated with pediatric brain injuries. Full article
(This article belongs to the Special Issue Drug Delivery across the Blood–Brain Barrier)
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