Drug Delivery across the Blood-Brain Barrier for the Treatment of Brain Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 10762

Special Issue Editors


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Guest Editor
Associate Professor, Department of Biology, University of Naples Federico II, 80126 Naples, Italy
Interests: cell biology; endocrinology; histology; neuropeptide cell line; drug delivery across blood-brain barrier; three-dimensional spheroids; light-sheet fluorescence microscopy; 3D deep tissue imaging; millifluidic culture
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Co-Guest Editor
Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy
Interests: antimicrobial peptide; self-assembling nanostructures based peptides; drug delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Blood-brain barrier (BBB) studies have greatly accelerated progress in precision medicine for brain diseases. However, much remains to be elucidated. The role of the BBB in the onset and progression of brain diseases has been only been partially clarified. Studies on BBB biology have not only provided insights into the mechanisms underlying its tight regulation of molecule traffic between blood and neural tissue but also suggested that the nature, structure, and functions of the BBB are even more complex than previously considered. Our knowledge in the drug delivery research field has been greatly improved by BBB studies. In addition, new groundbreaking technologies, such as 3D live imaging and in vitro fluidodynamic cell culture systems, have greatly expanded our knowledge in this field, permitting researchers to study and demonstrate, at least in part, the involvement of the BBB in the main brain diseases. This Special Issue focuses on recent advances in the discovery, characterization, translation, and application of drug delivery across the BBB. The aim is to stimulate research interest in this field toward both improving the existing while developing new strategies for efficient drug delivery across BBB, which will be useful for the treatment of brain diseases.

Prof. Salvatore Valiante
Guest Editor
Dr. Annarita Falanga
Co-Guest Editor

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Keywords

  • drug delivery
  • brain disease
  • neurodegeneration
  • neurovascular unit
  • brain barrier
  • neurocytology
  • brain endothelial cell
  • pericyte
  • glia
  • central nervous system
  • in vitro system
  • brain imaging

Published Papers (3 papers)

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Research

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21 pages, 3986 KiB  
Article
Neuroprotective Effects of gH625-lipoPACAP in an In Vitro Fluid Dynamic Model of Parkinson’s Disease
by Teresa Barra, Annarita Falanga, Rosa Bellavita, Jessica Pisano, Vincenza Laforgia, Marina Prisco, Stefania Galdiero and Salvatore Valiante
Biomedicines 2022, 10(10), 2644; https://doi.org/10.3390/biomedicines10102644 - 20 Oct 2022
Cited by 2 | Viewed by 1741
Abstract
Parkinson’s disease (PD) is an aggressive and devastating age-related disorder. Although the causes are still unclear, several factors, including genetic and environmental, are involved. Except for symptomatic drugs, there are not, to date, any real cures for PD. For this purpose, it is [...] Read more.
Parkinson’s disease (PD) is an aggressive and devastating age-related disorder. Although the causes are still unclear, several factors, including genetic and environmental, are involved. Except for symptomatic drugs, there are not, to date, any real cures for PD. For this purpose, it is necessary develop a model to better study this disease. Neuroblastoma cell line, SH-SY5Y, differentiated with retinoic acid represents a good in vitro model to explore PD, since it maintains growth cells to differentiated neurons. In the present study, SH-SY5Y cells were treated with 1-methyl-4-phenylpyridinium (MPP+), a neurotoxin that induces Parkinsonism, and the neuroprotective effects of pituitary adenylate cyclase-activating polypeptide (PACAP), delivered by functionalized liposomes in a blood–brain barrier fluid dynamic model, were evaluated. We demonstrated PACAP neuroprotective effects when delivered by gH625-liposome on MPP+-damaged SH-SY5Y spheroids. Full article
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18 pages, 1760 KiB  
Article
High-Frequency Irreversible Electroporation (H-FIRE) Induced Blood–Brain Barrier Disruption Is Mediated by Cytoskeletal Remodeling and Changes in Tight Junction Protein Regulation
by Brittanie R. Partridge, Yukitaka Kani, Melvin F. Lorenzo, Sabrina N. Campelo, Irving C. Allen, Jonathan Hinckley, Fang-Chi Hsu, Scott S. Verbridge, John L. Robertson, Rafael V. Davalos and John H. Rossmeisl
Biomedicines 2022, 10(6), 1384; https://doi.org/10.3390/biomedicines10061384 - 11 Jun 2022
Cited by 9 | Viewed by 2518
Abstract
Glioblastoma is the deadliest malignant brain tumor. Its location behind the blood–brain barrier (BBB) presents a therapeutic challenge by preventing effective delivery of most chemotherapeutics. H-FIRE is a novel tumor ablation method that transiently disrupts the BBB through currently unknown mechanisms. We hypothesized [...] Read more.
Glioblastoma is the deadliest malignant brain tumor. Its location behind the blood–brain barrier (BBB) presents a therapeutic challenge by preventing effective delivery of most chemotherapeutics. H-FIRE is a novel tumor ablation method that transiently disrupts the BBB through currently unknown mechanisms. We hypothesized that H-FIRE mediated BBB disruption (BBBD) occurs via cytoskeletal remodeling and alterations in tight junction (TJ) protein regulation. Intracranial H-FIRE was delivered to Fischer rats prior to sacrifice at 1-, 24-, 48-, 72-, and 96 h post-treatment. Cytoskeletal proteins and native and ubiquitinated TJ proteins (TJP) were evaluated using immunoprecipitation, Western blotting, and gene-expression arrays on treated and sham control brain lysates. Cytoskeletal and TJ protein expression were further evaluated with immunofluorescent microscopy. A decrease in the F/G-actin ratio, decreased TJP concentrations, and increased ubiquitination of TJP were observed 1–48 h post-H-FIRE compared to sham controls. By 72–96 h, cytoskeletal and TJP expression recovered to pretreatment levels, temporally corresponding with increased claudin-5 and zonula occludens-1 gene expression. Ingenuity pathway analysis revealed significant dysregulation of claudin genes, centered around claudin-6 in H-FIRE treated rats. In conclusion, H-FIRE is capable of permeating the BBB in a spatiotemporal manner via cytoskeletal-mediated TJP modulation. This minimally invasive technology presents with applications for localized and long-lived enhanced intracranial drug delivery. Full article
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Review

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26 pages, 810 KiB  
Review
Drug Delivery Challenges in Brain Disorders across the Blood–Brain Barrier: Novel Methods and Future Considerations for Improved Therapy
by Aneesha Achar, Rosemary Myers and Chaitali Ghosh
Biomedicines 2021, 9(12), 1834; https://doi.org/10.3390/biomedicines9121834 - 4 Dec 2021
Cited by 38 | Viewed by 5434
Abstract
Due to the physiological and structural properties of the blood–brain barrier (BBB), the delivery of drugs to the brain poses a unique challenge in patients with central nervous system (CNS) disorders. Several strategies have been investigated to circumvent the barrier for CNS therapeutics [...] Read more.
Due to the physiological and structural properties of the blood–brain barrier (BBB), the delivery of drugs to the brain poses a unique challenge in patients with central nervous system (CNS) disorders. Several strategies have been investigated to circumvent the barrier for CNS therapeutics such as in epilepsy, stroke, brain cancer and traumatic brain injury. In this review, we summarize current and novel routes of drug interventions, discuss pharmacokinetics and pharmacodynamics at the neurovascular interface, and propose additional factors that may influence drug delivery. At present, both technological and mechanistic tools are devised to assist in overcoming the BBB for more efficient and improved drug bioavailability in the treatment of clinically devastating brain disorders. Full article
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