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Pharmaceutics
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Crossing the Blood–Brain Barrier and Targeting the Brain to Meet...
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Crossing the Blood–Brain Barrier and Targeting the Brain to Meet the Challenge of CNS Diseases

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

Deadline for manuscript submissions: closed (25 November 2022) | Viewed by 6770

Special Issue Editor

Prof. Dr. Aikaterini Lalatsa

E-Mail Website
Guest Editor
School of Pharmacy and Biomedical Sciences, John Arbuthnot Building, Robertson Wing, University of Strathclyde, 161 Cathedral Street, Glasgow G1 1LG, UK
Interests: nanomedicines; polymers; peptides; neglected diseases; targeted delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Brain diseases affect one in three people worldwide, and nano-enabled and nose-to-brain strategies are paving the way towards novel therapies that can meet the challenge of brain diseases.

This Special Issue aims to focus on nano-enabled and nose-to-brain strategies as well as in vitro models for understanding permeability across the blood–brain barrier.

We invite articles on all aspects of drug discovery, delivery, and targeting across the blood–brain barrier and nose-to-brain delivery as well as in vitro and lab-on-chip models for the blood–brain barrier.

Prof. Dr. Aikaterini Lalatsa
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. 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

  • brain targeting
  • nanomedicines
  • drug conjugates
  • nose-to-brain delivery
  • brain diseases and tumors
  • in vitro nasal and blood-barrier models

Published Papers (3 papers)

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Research

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0 pages, 4041 KiB  
Article
Development and Comparative In Vitro and In Vivo Study of BNN27 Mucoadhesive Liposomes and Nanoemulsions for Nose-to-Brain Delivery
by Maria Kannavou, Kanelina Karali, Theodora Katsila, Eleni Siapi, Antonia Marazioti, Pavlos Klepetsanis, Theodora Calogeropoulou, Ioannis Charalampopoulos and Sophia G. Antimisiaris
Pharmaceutics 2023, 15(2), 419; https://doi.org/10.3390/pharmaceutics15020419 - 27 Jan 2023
Cited by 3 | Viewed by 1315
Abstract
Intranasal administration offers an alternative and promising approach for direct nose-to-brain delivery. Herein, we developed two chitosan (CHT)-coated (and uncoated) nanoformulations of BNN27 (a synthetic C-17-spiro-dehydroepiandrosterone analogue), liposomes (LIPs), and nanoemulsions (NEs), and compared their properties and brain disposition (in vitro and in [...] Read more.
Intranasal administration offers an alternative and promising approach for direct nose-to-brain delivery. Herein, we developed two chitosan (CHT)-coated (and uncoated) nanoformulations of BNN27 (a synthetic C-17-spiro-dehydroepiandrosterone analogue), liposomes (LIPs), and nanoemulsions (NEs), and compared their properties and brain disposition (in vitro and in vivo). LIPs were formulated by thin film hydration and coated with CHT by dropwise addition. BNN27-loaded NEs (BNEs) were developed by spontaneous emulsification and optimized for stability and mucoadhesive properties. Mucoadhesive properties were evaluated by mucin adherence. Negatively charged CHT-coated LIPs (with 0.1% CHT/lipid) demonstrated the highest coating efficiency and mucoadhesion. BNEs containing 10% w/w Capmul-MCM and 0.3% w/w CHT demonstrated the optimal properties. Transport of LIP or NE-associated rhodamine-lipid across the blood–brain barrier (in vitro) was significantly higher for NEs compared to LIPs, and the CHT coating demonstrated a negative effect on transport. However, the CHT-coated BNEs demonstrated higher and faster in vivo brain disposition following intranasal administration compared to CHT-LIPs. For both BNEs and LIPs, CHT-coating resulted in the increased (in vivo) brain disposition of BNN27. Current results prove that CHT-coated NEs consisting of compatible nasal administration ingredients succeeded in to delivering more BNN27 to the brain (and faster) compared to the CHT-coated LIPs. Full article
(This article belongs to the Special Issue Crossing the Blood–Brain Barrier and Targeting the Brain to Meet the Challenge of CNS Diseases)
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14 pages, 806 KiB  
Article
Intranasal Administration of N-acetyl-L-cysteine Combined with Cell-Penetrating Peptide-Modified Polymer Nanomicelles as a Potential Therapeutic Approach for Amyotrophic Lateral Sclerosis
by Takumi Kurano, Takanori Kanazawa, Shingo Iioka, Hiromu Kondo, Yasuhiro Kosuge and Toyofumi Suzuki
Pharmaceutics 2022, 14(12), 2590; https://doi.org/10.3390/pharmaceutics14122590 - 24 Nov 2022
Cited by 8 | Viewed by 1991
Abstract
Intranasal administration is a promising route for direct drug delivery to the brain; its combination with nanocarriers enhances delivery. We have previously shown that intranasal administration combined with PEG-PCL-Tat (a nanocarrier) efficiently delivers drugs to the brain and exhibits excellent therapeutic efficacy against [...] Read more.
Intranasal administration is a promising route for direct drug delivery to the brain; its combination with nanocarriers enhances delivery. We have previously shown that intranasal administration combined with PEG-PCL-Tat (a nanocarrier) efficiently delivers drugs to the brain and exhibits excellent therapeutic efficacy against brain diseases. We aimed to clarify whether intranasal administration combined with PEG-PCL-Tat represents a useful drug delivery system (DDS) for amyotrophic lateral sclerosis (ALS) pharmacotherapy. We used N-acetyl-L-cysteine (NAC) as a model drug with low transferability to the spinal cord and determined the physicochemical properties of NAC/PEG-PCL-Tat. After intranasal administration of NAC/PEG-PCL-Tat, we measured the survival duration of superoxide dismutase-1 G93A mutant transgenic mice (G93A mice), widely used in ALS studies, and quantitatively analyzed the tissue distribution of NAC/PEG-PCL-Tat in ddY mice. The mean particle size and zeta potential of NAC/PEG-PCL-Tat were 294 nm and + 9.29 mV, respectively. Treatment with repeated intranasal administration of NAC/PEG-PCL-Tat considerably prolonged the median survival of G93A mice by 11.5 days compared with that of untreated G93A mice. Moreover, the highest distribution after a single administration of NAC/PEG-PCL-Tat was measured in the spinal cord. These results suggest that intranasal administration combined with PEG-PCL-Tat might represent a useful DDS for ALS therapeutics. Full article
(This article belongs to the Special Issue Crossing the Blood–Brain Barrier and Targeting the Brain to Meet the Challenge of CNS Diseases)
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Review

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38 pages, 1239 KiB  
Review
In Vitro Models of the Blood–Cerebrospinal Fluid Barrier and Their Applications in the Development and Research of (Neuro)Pharmaceuticals
by Fatemeh Dabbagh, Horst Schroten and Christian Schwerk
Pharmaceutics 2022, 14(8), 1729; https://doi.org/10.3390/pharmaceutics14081729 - 18 Aug 2022
Cited by 4 | Viewed by 2796
Abstract
The pharmaceutical research sector has been facing the challenge of neurotherapeutics development and its inherited high-risk and high-failure-rate nature for decades. This hurdle is partly attributable to the presence of brain barriers, considered both as obstacles and opportunities for the entry of drug [...] Read more.
The pharmaceutical research sector has been facing the challenge of neurotherapeutics development and its inherited high-risk and high-failure-rate nature for decades. This hurdle is partly attributable to the presence of brain barriers, considered both as obstacles and opportunities for the entry of drug substances. The blood–cerebrospinal fluid (CSF) barrier (BCSFB), an under-studied brain barrier site compared to the blood–brain barrier (BBB), can be considered a potential therapeutic target to improve the delivery of CNS therapeutics and provide brain protection measures. Therefore, leveraging robust and authentic in vitro models of the BCSFB can diminish the time and effort spent on unproductive or redundant development activities by a preliminary assessment of the desired physiochemical behavior of an agent toward this barrier. To this end, the current review summarizes the efforts and progresses made to this research area with a notable focus on the attribution of these models and applied techniques to the pharmaceutical sector and the development of neuropharmacological therapeutics and diagnostics. A survey of available in vitro models, with their advantages and limitations and cell lines in hand will be provided, followed by highlighting the potential applications of such models in the (neuro)therapeutics discovery and development pipelines. Full article
(This article belongs to the Special Issue Crossing the Blood–Brain Barrier and Targeting the Brain to Meet the Challenge of CNS Diseases)
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