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Pharmaceutics
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Non-invasive Device-Mediated Brain Drug Delivery across the Blood-Brain Barrier
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Non-invasive Device-Mediated Brain Drug Delivery across the Blood-Brain Barrier

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

Deadline for manuscript submissions: closed (20 December 2023) | Viewed by 22694

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Nicolas Tournier

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Guest Editor
Laboratoire d’Imagerie Biomédicale Multimodale, BIOMAPS, Université Paris-Saclay, CEA, CNRS, Inserm, Service Hospitalier Frédéric Joliot, 4 Place du Général Leclerc, 91401 Orsay, France
Interests: blood-brain barrier; organic anion transporters; breast cancer resistance protein; vanadate-sensitive ATPase; multiple drug resistance
Special Issues, Collections and Topics in MDPI journals
Dr. Toshihiko Tashima

E-Mail
Guest Editor
Tashima Laboratories of Arts and Sciences, 1239-5 Toriyama-cho, Kohoku-ku, Yokohama 222-0035, Japan
Interests: drug design; drug discovery; pharmacophore; drug delivery; organic synthesis; drug cell-membrane permeability; pharmaceutical sciences; medicinal chemistry; chemical biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We will be serving as the Guest Editor for this very interesting Special Issue on “Non-Invasive Device-Mediated Brain Drug Delivery Across the Blood–Brain Barrier”. It is well-known that the blood–brain barrier (BBB), substantially composed of tight junctions between the capillary endothelial cells and efflux transporters such as MDR1 at the apical membrane of the capillary endothelial cells, prevents drugs from entering the brain. Accordingly, drug delivery into the brain across the BBB is a challenging task, particularly in central nervous system diseases such as Alzheimer’s disease and Parkinson’s disease as well as brain cancers such as glioma. It is true that drugs in systemic circulation go through intentional membrane disruption or intentional tight junction disruption into the brain across the BBB, but bystander harmful compounds can enter the brain together. Moreover, although craniotomy is often conducted for surgical removal or direct drug administration, this process burdens and torments patients. Thus, non-invasive, device-mediated brain drug delivery across the BBB should be developed to improve not only patient health, but also quality of life. At present, brain drug delivery systems that utilize biological transport machineries such as carrier-mediated transport, receptor-mediated transcytosis, lipid-raft-mediated transcytosis, or macropinocytosis at the BBB have been extensively investigated. This Special Issue aims to share recent progress and trends in this field. We welcome submissions of all types of original articles concerned with noninvasive drug delivery into the brain across the BBB.

Topics include, but are not limited to, the strategies outlined below:

˗ Carrier-mediated transport

  • Drugs containing transporter recognition unit;
  • Substrate–drug conjugates with cleavable linkers.

˗ Receptor-mediated transcytosis

  • Antibody-drug conjugates with cleavable or uncleavable linkers;
  • Bispecific antibodies as antibody drugs;
  • Ligand-drug conjugates using ligands such as cell-penetrating peptides or homing peptides;
  • Drug-encapsulated nanoparticles covered with ligands using nanodelivery systems.

˗ Other strategies

Dr. Nicolas Tournier
Dr. Toshihiko Tashima
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

  • drug delivery systems
  • the blood-brain barrier (BBB)
  • non-invasive brain drug delivery
  • nanodelivery systems
  • transporter-consciously designed drug
  • carrier-mediated transport
  • receptor-mediated transcytosis
  • central nervous system disease
  • Alzheimer's disease (AD)
  • Parkinson's disease (PD)
  • brain cancer

Published Papers (11 papers)

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Editorial

Jump to: Research, Review

6 pages, 213 KiB  
Editorial
Non-Invasive Device-Mediated Drug Delivery to the Brain across the Blood–Brain Barrier
by Toshihiko Tashima and Nicolas Tournier
Pharmaceutics 2024, 16(3), 361; https://doi.org/10.3390/pharmaceutics16030361 - 05 Mar 2024
Viewed by 839
Abstract
We will be serving as the Guest Editor for this very interesting Special Issue on “Non-Invasive Device-Mediated Drug Delivery to the Brain Across the Blood–Brain Barrier” [...] Full article
(This article belongs to the Special Issue Non-invasive Device-Mediated Brain Drug Delivery across the Blood-Brain Barrier)

Research

Jump to: Editorial, Review

19 pages, 4429 KiB  
Article
Influence of Surface Ligand Density and Particle Size on the Penetration of the Blood–Brain Barrier by Porous Silicon Nanoparticles
by Weisen Zhang, Douer Zhu, Ziqiu Tong, Bo Peng, Xuan Cheng, Lars Esser and Nicolas H. Voelcker
Pharmaceutics 2023, 15(9), 2271; https://doi.org/10.3390/pharmaceutics15092271 - 03 Sep 2023
Cited by 4 | Viewed by 1299
Abstract
Overcoming the blood–brain barrier (BBB) remains a significant challenge with regard to drug delivery to the brain. By incorporating targeting ligands, and by carefully adjusting particle sizes, nanocarriers can be customized to improve drug delivery. Among these targeting ligands, transferrin stands out due [...] Read more.
Overcoming the blood–brain barrier (BBB) remains a significant challenge with regard to drug delivery to the brain. By incorporating targeting ligands, and by carefully adjusting particle sizes, nanocarriers can be customized to improve drug delivery. Among these targeting ligands, transferrin stands out due to the high expression level of its receptor (i.e., transferrin receptor) on the BBB. Porous silicon nanoparticles (pSiNPs) are a promising drug nanocarrier to the brain due to their biodegradability, biocompatibility, and exceptional drug-loading capacity. However, an in-depth understanding of the optimal nanoparticle size and transferrin surface density, in order to maximize BBB penetration, is still lacking. To address this gap, a diverse library of pSiNPs was synthesized using bifunctional poly(ethylene glycol) linkers with methoxy or/and carboxyl terminal groups. These variations allowed us to explore different transferrin surface densities in addition to particle sizes. The effects of these parameters on the cellular association, uptake, and transcytosis in immortalized human brain microvascular endothelial cells (hCMEC/D3) were investigated using multiple in vitro systems of increasing degrees of complexity. These systems included the following: a 2D cell culture, a static Transwell model, and a dynamic BBB-on-a-chip model. Our results revealed the significant impact of both the ligand surface density and size of pSiNPs on their ability to penetrate the BBB, wherein intermediate-level transferrin densities and smaller pSiNPs exhibited the highest BBB transportation efficiency in vitro. Moreover, notable discrepancies emerged between the tested in vitro assays, further emphasizing the necessity of using more physiologically relevant assays, such as a microfluidic BBB-on-a-chip model, for nanocarrier testing and evaluation. Full article
(This article belongs to the Special Issue Non-invasive Device-Mediated Brain Drug Delivery across the Blood-Brain Barrier)
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Graphical abstract

11 pages, 1368 KiB  
Communication
Novel Human/Non-Human Primate Cross-Reactive Anti-Transferrin Receptor Nanobodies for Brain Delivery of Biologics
by Laura Rué, Tom Jaspers, Isabelle M. S. Degors, Sam Noppen, Dominique Schols, Bart De Strooper and Maarten Dewilde
Pharmaceutics 2023, 15(6), 1748; https://doi.org/10.3390/pharmaceutics15061748 - 16 Jun 2023
Cited by 3 | Viewed by 1698
Abstract
The blood-brain barrier (BBB), while being the gatekeeper of the central nervous system (CNS), is a bottleneck for the treatment of neurological diseases. Unfortunately, most of the biologicals do not reach their brain targets in sufficient quantities. The antibody targeting of receptor-mediated transcytosis [...] Read more.
The blood-brain barrier (BBB), while being the gatekeeper of the central nervous system (CNS), is a bottleneck for the treatment of neurological diseases. Unfortunately, most of the biologicals do not reach their brain targets in sufficient quantities. The antibody targeting of receptor-mediated transcytosis (RMT) receptors is an exploited mechanism that increases brain permeability. We previously discovered an anti-human transferrin receptor (TfR) nanobody that could efficiently deliver a therapeutic moiety across the BBB. Despite the high homology between human and cynomolgus TfR, the nanobody was unable to bind the non-human primate receptor. Here we report the discovery of two nanobodies that were able to bind human and cynomolgus TfR, making these nanobodies more clinically relevant. Whereas nanobody BBB00515 bound cynomolgus TfR with 18 times more affinity than it did human TfR, nanobody BBB00533 bound human and cynomolgus TfR with similar affinities. When fused with an anti-beta-site amyloid precursor protein cleaving enzyme (BACE1) antibody (1A11AM), each of the nanobodies was able to increase its brain permeability after peripheral injection. A 40% reduction of brain Aβ1–40 levels could be observed in mice injected with anti-TfR/BACE1 bispecific antibodies when compared to vehicle-injected mice. In summary, we found two nanobodies that could bind both human and cynomolgus TfR with the potential to be used clinically to increase the brain permeability of therapeutic biologicals. Full article
(This article belongs to the Special Issue Non-invasive Device-Mediated Brain Drug Delivery across the Blood-Brain Barrier)
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23 pages, 4225 KiB  
Article
Non-Invasive, Targeted Nanoparticle-Mediated Drug Delivery across a Novel Human BBB Model
by Shona Kaya, Bridgeen Callan and Susan Hawthorne
Pharmaceutics 2023, 15(5), 1382; https://doi.org/10.3390/pharmaceutics15051382 - 30 Apr 2023
Cited by 2 | Viewed by 1792
Abstract
The blood–brain barrier (BBB) is a highly sophisticated system with the ability to regulate compounds transporting through the barrier and reaching the central nervous system (CNS). The BBB protects the CNS from toxins and pathogens but can cause major issues when developing novel [...] Read more.
The blood–brain barrier (BBB) is a highly sophisticated system with the ability to regulate compounds transporting through the barrier and reaching the central nervous system (CNS). The BBB protects the CNS from toxins and pathogens but can cause major issues when developing novel therapeutics to treat neurological disorders. PLGA nanoparticles have been developed to successfully encapsulate large hydrophilic compounds for drug delivery. Within this paper, we discuss the encapsulation of a model compound Fitc-dextran, a large molecular weight (70 kDa), hydrophilic compound, with over 60% encapsulation efficiency (EE) within a PLGA nanoparticle (NP). The NP surface was chemically modified with DAS peptide, a ligand that we designed which has an affinity for nicotinic receptors, specifically alpha 7 nicotinic receptors, found on the surface of brain endothelial cells. The attachment of DAS transports the NP across the BBB by receptor-mediated transcytosis (RMT). Assessment of the delivery efficacy of the DAS-conjugated Fitc-dextran-loaded PLGA NP was studied in vitro using our optimal triculture in vitro BBB model, which successfully replicates the in vivo BBB environment, producing high TEER (≥230 ) and high expression of ZO1 protein. Utilising our optimal BBB model, we successfully transported fourteen times the concentration of DAS-Fitc-dextran-PLGA NP compared to non-conjugated Fitc-dextran-PLGA NP. Our novel in vitro model is a viable method of high-throughput screening of potential therapeutic delivery systems to the CNS, such as our receptor-targeted DAS ligand-conjugated NP, whereby only lead therapeutic compounds will progress to in vivo studies. Full article
(This article belongs to the Special Issue Non-invasive Device-Mediated Brain Drug Delivery across the Blood-Brain Barrier)
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17 pages, 3817 KiB  
Article
Self-Assembled Lecithin-Chitosan Nanoparticles Improved Rotigotine Nose-to-Brain Delivery and Brain Targeting Efficiency
by Paramita Saha, Prabhjeet Singh, Himanshu Kathuria, Deepak Chitkara and Murali Monohar Pandey
Pharmaceutics 2023, 15(3), 851; https://doi.org/10.3390/pharmaceutics15030851 - 05 Mar 2023
Cited by 8 | Viewed by 2610
Abstract
Rotigotine (RTG) is a non-ergoline dopamine agonist and an approved drug for treating Parkinson’s disease. However, its clinical use is limited due to various problems, viz. poor oral bioavailability (<1%), low aqueous solubility, and extensive first-pass metabolism. In this study, rotigotine-loaded lecithin-chitosan nanoparticles [...] Read more.
Rotigotine (RTG) is a non-ergoline dopamine agonist and an approved drug for treating Parkinson’s disease. However, its clinical use is limited due to various problems, viz. poor oral bioavailability (<1%), low aqueous solubility, and extensive first-pass metabolism. In this study, rotigotine-loaded lecithin-chitosan nanoparticles (RTG-LCNP) were formulated to enhance its nose-to-brain delivery. RTG-LCNP was prepared by self-assembly of chitosan and lecithin due to ionic interactions. The optimized RTG-LCNP had an average diameter of 108 nm with 14.43 ± 2.77% drug loading. RTG-LCNP exhibited spherical morphology and good storage stability. Intranasal RTG-LCNP improved the brain availability of RTG by 7.86 fold with a 3.84-fold increase in the peak brain drug concentration (Cmax(brain)) compared to intranasal drug suspensions. Further, the intranasal RTG-LCNP significantly reduced the peak plasma drug concentration (Cmax(plasma)) compared to intranasal RTG suspensions. The direct drug transport percentage (DTP (%)) of optimized RTG-LCNP was found to be 97.3%, which shows effective direct nose-to-brain drug uptake and good targeting efficiency. In conclusion, RTG-LCNP enhanced drug brain availability, showing the potential for clinical application. Full article
(This article belongs to the Special Issue Non-invasive Device-Mediated Brain Drug Delivery across the Blood-Brain Barrier)
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16 pages, 3629 KiB  
Article
Molecular Imaging of Ultrasound-Mediated Blood-Brain Barrier Disruption in a Mouse Orthotopic Glioblastoma Model
by Chiara Bastiancich, Samantha Fernandez, Florian Correard, Anthony Novell, Benoit Larrat, Benjamin Guillet and Marie-Anne Estève
Pharmaceutics 2022, 14(10), 2227; https://doi.org/10.3390/pharmaceutics14102227 - 19 Oct 2022
Cited by 3 | Viewed by 2437
Abstract
Glioblastoma (GBM) is an aggressive and malignant primary brain tumor. The blood-brain barrier (BBB) limits the therapeutic options available to tackle this incurable tumor. Transient disruption of the BBB by focused ultrasound (FUS) is a promising and safe approach to increase the brain [...] Read more.
Glioblastoma (GBM) is an aggressive and malignant primary brain tumor. The blood-brain barrier (BBB) limits the therapeutic options available to tackle this incurable tumor. Transient disruption of the BBB by focused ultrasound (FUS) is a promising and safe approach to increase the brain and tumor concentration of drugs administered systemically. Non-invasive, sensitive, and reliable imaging approaches are required to better understand the impact of FUS on the BBB and brain microenvironment. In this study, nuclear imaging (SPECT/CT and PET/CT) was used to quantify neuroinflammation 48 h post-FUS and estimate the influence of FUS on BBB opening and tumor growth in vivo. BBB disruptions were performed on healthy and GBM-bearing mice (U-87 MG xenograft orthotopic model). The BBB recovery kinetics were followed and quantified by [99mTc]Tc-DTPA SPECT/CT imaging at 0.5 h, 3 h and 24 h post-FUS. The absence of neuroinflammation was confirmed by [18F]FDG PET/CT imaging 48 h post-FUS. The presence of the tumor and its growth were evaluated by [68Ga]Ga-RGD2 PET/CT imaging and post-mortem histological analysis, showing that tumor growth was not influenced by FUS. In conclusion, molecular imaging can be used to evaluate the time frame for systemic treatment combined with transient BBB opening and to test its efficacy over time. Full article
(This article belongs to the Special Issue Non-invasive Device-Mediated Brain Drug Delivery across the Blood-Brain Barrier)
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Review

Jump to: Editorial, Research

16 pages, 1168 KiB  
Review
Mesenchymal Stem Cell (MSC)-Based Drug Delivery into the Brain across the Blood–Brain Barrier
by Toshihiko Tashima
Pharmaceutics 2024, 16(2), 289; https://doi.org/10.3390/pharmaceutics16020289 - 18 Feb 2024
Cited by 1 | Viewed by 1240
Abstract
At present, stem cell-based therapies using induced pluripotent stem cells (iPSCs) or mesenchymal stem cells (MSCs) are being used to explore the potential for regenerative medicine in the treatment of various diseases, owing to their ability for multilineage differentiation. Interestingly, MSCs are employed [...] Read more.
At present, stem cell-based therapies using induced pluripotent stem cells (iPSCs) or mesenchymal stem cells (MSCs) are being used to explore the potential for regenerative medicine in the treatment of various diseases, owing to their ability for multilineage differentiation. Interestingly, MSCs are employed not only in regenerative medicine, but also as carriers for drug delivery, homing to target sites in injured or damaged tissues including the brain by crossing the blood–brain barrier (BBB). In drug research and development, membrane impermeability is a serious problem. The development of central nervous system drugs for the treatment of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, remains difficult due to impermeability in capillary endothelial cells at the BBB, in addition to their complicated pathogenesis and pathology. Thus, intravenously or intraarterially administered MSC-mediated drug delivery in a non-invasive way is a solution to this transendothelial problem at the BBB. Substances delivered by MSCs are divided into artificially included materials in advance, such as low molecular weight compounds including doxorubicin, and expected protein expression products of genetic modification, such as interleukins. After internalizing into the brain through the fenestration between the capillary endothelial cells, MSCs release their cargos to the injured brain cells. In this review, I introduce the potential and advantages of drug delivery into the brain across the BBB using MSCs as a carrier that moves into the brain as if they acted of their own will. Full article
(This article belongs to the Special Issue Non-invasive Device-Mediated Brain Drug Delivery across the Blood-Brain Barrier)
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41 pages, 1165 KiB  
Review
Nose-to-Brain (N2B) Delivery: An Alternative Route for the Delivery of Biologics in the Management and Treatment of Central Nervous System Disorders
by Elizabeth J. Patharapankal, Adejumoke Lara Ajiboye, Claudia Mattern and Vivek Trivedi
Pharmaceutics 2024, 16(1), 66; https://doi.org/10.3390/pharmaceutics16010066 - 31 Dec 2023
Cited by 2 | Viewed by 1673
Abstract
In recent years, there have been a growing number of small and large molecules that could be used to treat diseases of the central nervous system (CNS). Nose-to-brain delivery can be a potential option for the direct transport of molecules from the nasal [...] Read more.
In recent years, there have been a growing number of small and large molecules that could be used to treat diseases of the central nervous system (CNS). Nose-to-brain delivery can be a potential option for the direct transport of molecules from the nasal cavity to different brain areas. This review aims to provide a compilation of current approaches regarding drug delivery to the CNS via the nose, with a focus on biologics. The review also includes a discussion on the key benefits of nasal delivery as a promising alternative route for drug administration and the involved pathways or mechanisms. This article reviews how the application of various auxiliary agents, such as permeation enhancers, mucolytics, in situ gelling/mucoadhesive agents, enzyme inhibitors, and polymeric and lipid-based systems, can promote the delivery of large molecules in the CNS. The article also includes a discussion on the current state of intranasal formulation development and summarizes the biologics currently in clinical trials. It was noted that significant progress has been made in this field, and these are currently being applied to successfully transport large molecules to the CNS via the nose. However, a deep mechanistic understanding of this route, along with the intimate knowledge of various excipients and their interactions with the drug and nasal physiology, is still necessary to bring us one step closer to developing effective formulations for nasal–brain drug delivery. Full article
(This article belongs to the Special Issue Non-invasive Device-Mediated Brain Drug Delivery across the Blood-Brain Barrier)
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28 pages, 1900 KiB  
Review
Non-Invasive Drug Delivery across the Blood–Brain Barrier: A Prospective Analysis
by Sarfaraz K. Niazi
Pharmaceutics 2023, 15(11), 2599; https://doi.org/10.3390/pharmaceutics15112599 - 07 Nov 2023
Cited by 3 | Viewed by 1983
Abstract
Non-invasive drug delivery across the blood–brain barrier (BBB) represents a significant advancement in treating neurological diseases. The BBB is a tightly packed layer of endothelial cells that shields the brain from harmful substances in the blood, allowing necessary nutrients to pass through. It [...] Read more.
Non-invasive drug delivery across the blood–brain barrier (BBB) represents a significant advancement in treating neurological diseases. The BBB is a tightly packed layer of endothelial cells that shields the brain from harmful substances in the blood, allowing necessary nutrients to pass through. It is a highly selective barrier, which poses a challenge to delivering therapeutic agents into the brain. Several non-invasive procedures and devices have been developed or are currently being investigated to enhance drug delivery across the BBB. This paper presents a review and a prospective analysis of the art and science that address pharmacology, technology, delivery systems, regulatory approval, ethical concerns, and future possibilities. Full article
(This article belongs to the Special Issue Non-invasive Device-Mediated Brain Drug Delivery across the Blood-Brain Barrier)
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27 pages, 2651 KiB  
Review
Cell-Penetrating and Targeted Peptides Delivery Systems as Potential Pharmaceutical Carriers for Enhanced Delivery across the Blood–Brain Barrier (BBB)
by Soma Mondal Ghorai, Auroni Deep, Devanshi Magoo, Chetna Gupta and Nikesh Gupta
Pharmaceutics 2023, 15(7), 1999; https://doi.org/10.3390/pharmaceutics15071999 - 21 Jul 2023
Cited by 11 | Viewed by 3719
Abstract
Among the challenges to the 21st-century health care industry, one that demands special mention is the transport of drugs/active pharmaceutical agents across the blood–brain barrier (BBB). The epithelial-like tight junctions within the brain capillary endothelium hinder the uptake of most pharmaceutical agents. With [...] Read more.
Among the challenges to the 21st-century health care industry, one that demands special mention is the transport of drugs/active pharmaceutical agents across the blood–brain barrier (BBB). The epithelial-like tight junctions within the brain capillary endothelium hinder the uptake of most pharmaceutical agents. With an aim to understand more deeply the intricacies of cell-penetrating and targeted peptides as a powerful tool for desirable biological activity, we provide a critical review of both CPP and homing/targeted peptides as intracellular drug delivery agents, especially across the blood–brain barrier (BBB). Two main peptides have been discussed to understand intracellular drug delivery; first is the cell-penetrating peptides (CPPs) for the targeted delivery of compounds of interest (primarily peptides and nucleic acids) and second is the family of homing peptides, which specifically targets cells/tissues based on their overexpression of tumour-specific markers and are thus at the heart of cancer research. These small, amphipathic molecules demonstrate specific physical and chemical modifications aimed at increased ease of cellular internalisation. Because only a limited number of drug molecules can bypass the blood–brain barrier by free diffusion, it is essential to explore all aspects of CPPs that can be exploited for crossing this barrier. Considering siRNAs that can be designed against any target RNA, marking such molecules with high therapeutic potential, we present a synopsis of the studies on synthetic siRNA-based therapeutics using CPPs and homing peptides drugs that can emerge as potential drug-delivery systems as an upcoming requirement in the world of pharma- and nutraceuticals. Full article
(This article belongs to the Special Issue Non-invasive Device-Mediated Brain Drug Delivery across the Blood-Brain Barrier)
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Graphical abstract

26 pages, 2974 KiB  
Review
Nanoparticle Strategies to Improve the Delivery of Anticancer Drugs across the Blood–Brain Barrier to Treat Brain Tumors
by Wouter J. F. Vanbilloen, Julian S. Rechberger, Jacob B. Anderson, Leo F. Nonnenbroich, Liang Zhang and David J. Daniels
Pharmaceutics 2023, 15(7), 1804; https://doi.org/10.3390/pharmaceutics15071804 - 23 Jun 2023
Cited by 4 | Viewed by 1739
Abstract
Primary brain and central nervous system (CNS) tumors are a diverse group of neoplasms that occur within the brain and spinal cord. Although significant advances in our understanding of the intricate biological underpinnings of CNS neoplasm tumorigenesis and progression have been made, the [...] Read more.
Primary brain and central nervous system (CNS) tumors are a diverse group of neoplasms that occur within the brain and spinal cord. Although significant advances in our understanding of the intricate biological underpinnings of CNS neoplasm tumorigenesis and progression have been made, the translation of these discoveries into effective therapies has been stymied by the unique challenges presented by these tumors’ exquisitely sensitive location and the body’s own defense mechanisms (e.g., the brain–CSF barrier and blood–brain barrier), which normally protect the CNS from toxic insult. These barriers effectively prevent the delivery of therapeutics to the site of disease. To overcome these obstacles, new methods for therapeutic delivery are being developed, with one such approach being the utilization of nanoparticles. Here, we will cover the current state of the field with a particular focus on the challenges posed by the BBB, the different nanoparticle classes which are under development for targeted CNS tumor therapeutics delivery, and strategies which have been developed to bypass the BBB and enable effective therapeutics delivery to the site of disease. Full article
(This article belongs to the Special Issue Non-invasive Device-Mediated Brain Drug Delivery across the Blood-Brain Barrier)
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