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Biomedicines
Special Issues
Targeted Drug Delivery to Brain
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Targeted Drug Delivery to Brain

A special issue of Biomedicines (ISSN 2227-9059).

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 15355

Special Issue Editor

Dr. Anjali Sharma

E-Mail Website
Guest Editor
Department of Chemistry, Washington State University, Pullman, WA 99164-4630, USA
Interests: brain delivery; drug/gene delivery; brain imaging; targeting; nanotechnology; central nervous system barriers; targeted drug delivery; cell-therapy; gene-therapy; polymeric nanocarriers

Special Issue Information

Dear Colleagues,

Neurological disorders affect millions of people worldwide, leading to an increased global healthcare burden. The poor transport of therapeutics across various central nervous system barriers is a primary clinical challenge in the development of treatments for brain diseases. As a result, the majority of drugs for neurological diseases need to be administered at high doses, leading to systemic side effects and toxicities. The delivery of existing drugs in a targeted and superior fashion may offer great potential. Recent developments in the area of targeted brain-delivery strategies using nanotechnology, gene-therapy and cell-based therapeutics have shown significant promise for enhancing the efficacy and safety of drugs by specifically delivering them to targeted locations in the brain. This Special Issue of Biomedicines focuses on the recent advancements in the field of brain drug and gene-delivery strategies aiming for delivery to specific regions, cells, and sub-cellular locations within the brain for the treatment of unmet clinical needs in the area of neurological diseases. We invite original research and review articles focusing on the challenges associated with drug delivery across the brain and the development of nanoparticles or biologics-based brain-targeted platforms for drug-/gene-delivery, imaging, and diagnostic applications.

Dr. Anjali Sharma
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. Biomedicines 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 2600 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

  • brain delivery
  • drug/gene delivery
  • brain imaging
  • targeting
  • nanotechnology
  • central nervous system barriers
  • targeted drug delivery
  • cell-therapy
  • gene-therapy
  • polymeric nanocarriers

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Published Papers (4 papers)

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Research

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13 pages, 3707 KiB  
Article
Assessment of Hyperosmolar Blood–Brain Barrier Opening in Glioblastoma via Histology with Evans Blue and DCE-MRI
by Jérôme Conq, Nicolas Joudiou, Bernard Ucakar, Kevin Vanvarenberg, Véronique Préat and Bernard Gallez
Biomedicines 2023, 11(7), 1957; https://doi.org/10.3390/biomedicines11071957 - 11 Jul 2023
Cited by 5 | Viewed by 2529
Abstract
Background: While the blood–brain barrier (BBB) is often compromised in glioblastoma (GB), the perfusion and consequent delivery of drugs are highly heterogeneous. Moreover, the accessibility of drugs is largely impaired in the margins of the tumor and for infiltrating cells at the origin [...] Read more.
Background: While the blood–brain barrier (BBB) is often compromised in glioblastoma (GB), the perfusion and consequent delivery of drugs are highly heterogeneous. Moreover, the accessibility of drugs is largely impaired in the margins of the tumor and for infiltrating cells at the origin of tumor recurrence. In this work, we evaluate the value of methods to assess hemodynamic changes induced by a hyperosmolar shock in the core and the margins of a tumor in a GB model. Methods: Osmotic shock was induced with an intracarotid infusion of a hypertonic solution of mannitol in mice grafted with U87-MG cells. The distribution of fluorescent dye (Evans blue) within the brain was assessed via histology. Dynamic contrast-enhanced (DCE)-MRI with an injection of Gadolinium-DOTA as the contrast agent was also used to evaluate the effect on hemodynamic parameters and the diffusion of the contrast agent outside of the tumor area. Results: The histological study revealed that the fluorescent dye diffused much more largely outside of the tumor area after osmotic shock than in control tumors. However, the study of tumor hemodynamic parameters via DCE-MRI did not reveal any change in the permeability of the BBB, whatever the studied MRI parameter. Conclusions: The use of hypertonic mannitol infusion seems to be a promising method to increase the delivery of compounds in the margins of GB. Nevertheless, the DCE-MRI analysis method using gadolinium-DOTA as a contrast agent seems of limited value for determining the efficacy of opening the BBB in GB after osmotic shock. Full article
(This article belongs to the Special Issue Targeted Drug Delivery to Brain)
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Review

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15 pages, 673 KiB  
Review
Insights into Healthcare Professionals’ Perceptions and Attitudes toward Nanotechnological Device Application: What Is the Current Situation in Glioblastoma Research?
by Federica Ragucci, Francesca Sireci, Francesco Cavallieri, Jessica Rossi, Giuseppe Biagini, Giovanni Tosi, Chiara Lucchi, Rodolfo Molina-Pena, Natalia Helen Ferreira, Mariana Zarur, Alba Ferreiros, William Bourgeois, François Berger, Miguel Abal, Audrey Rousseau, Frank Boury, Carmen Alvarez-Lorenzo, Emmanuel Garcion, Anna Pisanello, Giacomo Pavesi, Corrado Iaccarino, Luca Ghirotto, Maria Chiara Bassi and Franco Valzaniaadd Show full author list remove Hide full author list
Biomedicines 2023, 11(7), 1854; https://doi.org/10.3390/biomedicines11071854 - 28 Jun 2023
Cited by 2 | Viewed by 2417
Abstract
Nanotechnology application in cancer treatment is promising and is likely to quickly spread worldwide in the near future. To date, most scientific studies on nanomaterial development have focused on deepening the attitudes of end users and experts, leaving clinical practice implications unexplored. Neuro-oncology [...] Read more.
Nanotechnology application in cancer treatment is promising and is likely to quickly spread worldwide in the near future. To date, most scientific studies on nanomaterial development have focused on deepening the attitudes of end users and experts, leaving clinical practice implications unexplored. Neuro-oncology might be a promising field for the application of nanotechnologies, especially for malignant brain tumors with a low-survival rate such as glioblastoma (GBM). As to improving patients’ quality of life and life expectancy, innovative treatments are worth being explored. Indeed, it is important to explore clinicians’ intention to use experimental technologies in clinical practice. In the present study, we conducted an exploratory review of the literature about healthcare workers’ knowledge and personal opinions toward nanomedicine. Our search (i) gives evidence for disagreement between self-reported and factual knowledge about nanomedicine and (ii) suggests the internet and television as main sources of information about current trends in nanomedicine applications, over scientific journals and formal education. Current models of risk assessment suggest time-saving cognitive and affective shortcuts, i.e., heuristics support both laypeople and experts in the decision-making process under uncertainty, whereas they might be a source of error. Whether the knowledge is poor, heuristics are more likely to occur and thus clinicians’ opinions and perspectives toward new technologies might be biased. Full article
(This article belongs to the Special Issue Targeted Drug Delivery to Brain)
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14 pages, 1799 KiB  
Review
A Review on Increasing the Targeting of PAMAM as Carriers in Glioma Therapy
by Xingyue Li, Wenjing Ta, Ruochen Hua, Jihong Song and Wen Lu
Biomedicines 2022, 10(10), 2455; https://doi.org/10.3390/biomedicines10102455 - 1 Oct 2022
Cited by 10 | Viewed by 2616
Abstract
Glioma is an invasive brain cancer, and it is difficult to achieve desired therapeutic effects due to the high postoperative recurrence rate and limited efficacy of drug therapy hindered by the biological barrier of brain tissue. Nanodrug delivery systems are of great interest, [...] Read more.
Glioma is an invasive brain cancer, and it is difficult to achieve desired therapeutic effects due to the high postoperative recurrence rate and limited efficacy of drug therapy hindered by the biological barrier of brain tissue. Nanodrug delivery systems are of great interest, and many efforts have been made to utilize them for glioma treatment. Polyamidoamine (PAMAM), a starburst dendrimer, provides malleable molecular size, functionalized molecular structure and penetrable brain barrier characteristics. Therefore, PAMAM-based nanodrug delivery systems (PAMAM DDS) are preferred for glioma treatment research. In this review, experimental studies on PAMAM DDS for glioma therapy were focused on and summarized. Emphasis was given to three major topics: methods of drug loading, linkers between drug/ligand and PAMAM and ligands of modified PAMAM. A strategy for well-designed PAMAM DDS for glioma treatment was proposed. Purposefully understanding the physicochemical and structural characteristics of drugs is necessary for selecting drug loading methods and achieving high drug loading capacity. Additionally, functional ligands contribute to achieving the brain targeting, brain penetration and low toxicity of PAMAM DDS. Furthermore, a brilliant linker facilitates multidrug combination and multifunctional PAMAM DDS. PAMAM DDS show excellent promise as drug vehicles and will be further studied for product development and safety evaluation. Full article
(This article belongs to the Special Issue Targeted Drug Delivery to Brain)
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18 pages, 1175 KiB  
Review
Micro- and Nanosized Carriers for Nose-to-Brain Drug Delivery in Neurodegenerative Disorders
by Radka Boyuklieva and Bissera Pilicheva
Biomedicines 2022, 10(7), 1706; https://doi.org/10.3390/biomedicines10071706 - 14 Jul 2022
Cited by 40 | Viewed by 6946
Abstract
Neurodegenerative disorders (NDs) have become a serious health problem worldwide due to the rapid increase in the number of people that are affected and the constantly aging population. Among all NDs, Alzheimer’s and Parkinson’s disease are the most common, and many efforts have [...] Read more.
Neurodegenerative disorders (NDs) have become a serious health problem worldwide due to the rapid increase in the number of people that are affected and the constantly aging population. Among all NDs, Alzheimer’s and Parkinson’s disease are the most common, and many efforts have been made in the development of effective and reliable therapeutic strategies. The intranasal route of drug administration offers numerous advantages, such as bypassing the blood–brain barrier and providing a direct entrance to the brain through the olfactory and trigeminal neurons. The present review summarizes the available information on recent advances in micro- and nanoscale nose-to-brain drug-delivery systems as a novel strategy for the treatment of Alzheimer’s and Parkinson’s disease. Specifically, polymer- and lipid-base micro- and nanoparticles have been studied as a feasible approach to increase the brain bioavailability of certain drugs. Furthermore, nanocomposites are discussed as a suitable formulation for administration into the nasal cavity. Full article
(This article belongs to the Special Issue Targeted Drug Delivery to Brain)
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