Article
Engineering, Biomedical
Xiufeng Ju, Tongtong Miao, Haiyan Chen, Jiang Ni, Liang Han
Summary: Mfsd2a plays a crucial role in regulating the transcytosis and permeability of the blood-brain barrier. Strategies involving priming nanoparticles and drug-loaded nanoparticles have shown promising results in enhancing BBB crossing efficiency and brain accumulation of therapeutics for breast cancer brain metastases.
ADVANCED HEALTHCARE MATERIALS
(2021)
Review
Nanoscience & Nanotechnology
Tianyou Liu, Qinglian Xie, Zaiquan Dong, Qiang Peng
Summary: The treatment of central nervous system disorders is challenging due to the presence of the blood-brain barrier (BBB). Nanoparticles-based drug delivery systems have shown great potential in overcoming the BBB and treating CNS diseases. This article summarizes the recent progress in nanoparticles-based systems for CNS delivery and discusses the prerequisites, drawbacks, and challenges of nanocarriers in this field, such as protein corona formation.
Article
Pharmacology & Pharmacy
Julia Georgieva, Moriah Katt, Zhou Ye, Benjamin J. Umlauf, Cody J. Wenthur, Eric Shusta
Summary: The restrictive nature of the brain vasculature limits the exposure of central nervous system (CNS) to blood-borne biotherapeutics. The use of receptor-mediated transcytosis (RMT) mechanisms in blood-brain barrier endothelial cells can increase the bioavailability of such therapeutics. The antibody 46.1 has been identified to accumulate in the mouse brain and can deliver drug cargo to the CNS, primarily through the cavernous sinus-arterial route.
Review
Pharmacology & Pharmacy
Liang Han
Summary: The blood-brain barrier tightly regulates substance transport into and out of the brain, but strategies to modulate the BBB have the potential to improve drug delivery and therapeutic efficacy against brain diseases. Various modulation strategies have been investigated, showing promising directions for future research.
Article
Nanoscience & Nanotechnology
Xu Liu, Tian Xia, Yiran Fang, Huaqin Zuo, Xiaoqing Dong, Peipei Xu, Jian Ouyang
Summary: This study developed a novel drug delivery system using exosomes as carriers to deliver drugs to tumor cells. By conjugating anti-CD22 antibody fragments and encapsulating doxorubicin, the system effectively crossed the blood-brain barrier and exhibited significant therapeutic effects on lymphoma cells.
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
(2022)
Review
Pharmacology & Pharmacy
Magdalena Markowicz-Piasecka, Patrycja Darlak, Agata Markiewicz, Joanna Sikora, Santosh Kumar Adla, Sreelatha Bagina, Kristiina M. Huttunen
Summary: This article reviews the approaches aiming to improve drug penetration into the central nervous system, including direct systemic delivery, invasive delivery, and novel drug delivery systems used at the nanoscale. However, further research is needed to assess the biocompatibility and safety of these new drug carriers.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2022)
Article
Multidisciplinary Sciences
Geok-Lin Chua, Bryan C. Tan, Randy Y. J. Loke, Menglan He, Cheen-Fei Chin, Bernice H. Wong, Alvin C. Y. Kuk, Mei Ding, Markus R. Wenk, Lan Guan, Federico Torta, David L. Silver
Summary: Mfsd2a is a sodium-dependent lysophosphatidylcholine transporter expressed at the blood-brain barrier that is crucial for omega-3 fatty acid transport and brain development. Although the transport mechanism of Mfsd2a has been proposed through cryo-EM structures, the biochem-ical evidence of flippase activity and sodium-dependent LPC inversion is still lacking. In this study, an in vitro assay using recombinant Mfsd2a reconstituted in liposomes was established to demonstrate the flipping of lysophosphatidylserine (LPS) from the outer to the inner leaflet of a membrane bilayer in a sodium-dependent manner. Through cryo-EM structures, mutagenesis, and cell-based transport assay, amino acid residues important for Mfsd2a activity were identified, providing direct biochemical evidence of Mfsd2a functioning as a lysolipid flippase.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Pharmacology & Pharmacy
Barbara Sanchez-Dengra, Isabel Gonzalez-Alvarez, Marival Bermejo, Marta Gonzalez-Alvarez
Summary: The blood-brain barrier restricts the access of substances to the central nervous system, hindering the treatment of brain and spinal cord pathologies. This study analyzes and comments on various strategies, both invasive and non-invasive, to enhance substance access to the central nervous system. Invasive techniques include direct injection and therapeutic opening of the blood-brain barrier, while non-invasive techniques involve alternative administration routes, inhibition of efflux transporters, chemical modification of molecules, and the use of nanocarriers. The combination of different strategies may be the most promising approach to increase substance access to the central nervous system.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Review
Medicine, Research & Experimental
Sofia Parrasia, Ildiko Szabo, Mario Zoratti, Lucia Biasutto
Summary: Central nervous system diseases are difficult to treat due to the blood-brain barrier (BBB), which prevents most drugs from reaching the brain. Peptides show promise in helping drugs cross the BBB and target the brain. However, there are challenges such as potential toxic effects, short in vivo lifespan, and inadequate drug levels in the brain.
MOLECULAR PHARMACEUTICS
(2022)
Review
Pharmacology & Pharmacy
Eun Seo Choi, Eric Shusta
Summary: The review focuses on known and emerging RMT systems, targeting antibody properties related to BBB trafficking, and antibody validation strategies. Clinical development of known RMT targeting systems and identifying novel BBB RMT targets are important strategies for treating CNS diseases. Expanding the identification of BBB RMT systems and targeting molecule engineering will greatly contribute to the treatment of neurological diseases.
EXPERT OPINION ON DRUG DELIVERY
(2023)
Review
Instruments & Instrumentation
Yang Gao, Jianwei Zhu, Huili Lu
Summary: Biologics are promising for treating central nervous system diseases, but the blood-brain barrier limits their delivery to the brain. Scientists have explored various strategies, such as receptor-mediated transcytosis, to overcome this limitation, with single domain antibodies emerging as a novel alternative targeting vector.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2021)
Article
Medicine, Research & Experimental
Yuan Meng, Dong Sun, Yiyan Qin, Xiaoyi Dong, Guangzuo Luo, Ying Liu
Summary: This study demonstrated that cell-penetrating peptides (CPPs) can enhance the transduction efficiency of AAV9, a promising vector for CNS diseases treatment, by facilitating its ability to cross the blood-brain barrier (BBB) and induce higher expression of target genes in the brain.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Review
Biotechnology & Applied Microbiology
Yang-Bao Miao, Wang Zhao, Gao Renchi, Ying Gong, Yi Shi
Summary: This article summarizes the challenges of central nervous system (CNS) tumor invasion and the hindrance of the blood-brain barrier (BBB) on brain tumor drug development. It also discusses the application and strategies of nanotechnology as drug carriers to overcome the BBB obstacle. Finally, the article proposes the customization of nanoparticles to improve the efficacy of brain tumor treatments.
JOURNAL OF NANOBIOTECHNOLOGY
(2023)
Review
Cell Biology
Zhidong He, Yanan Zhao, Jing Sun
Summary: Mfsd2a plays a crucial role in maintaining the integrity of the blood-brain barrier and transporting docosahexaenoic acid. It inhibits caveolae-mediated endocytosis in brain endothelial cells. Knockout of the Mfsd2a gene increases the permeability of the blood-brain barrier, reduces docosahexaenoic acid content, and is associated with neuron loss, resulting in microcephaly and cognitive impairment. It is considered a potential therapeutic target for drug delivery to the central nervous system.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Ya Wei, Xue Xia, Hanmei Li, Huile Gao
Summary: This review article discusses the application and challenges of receptor-mediated nanodrug delivery in crossing the blood-brain barrier. It highlights the importance of enhancing drug delivery efficiency to improve therapeutic effects. Factors affecting nanodrug delivery efficiency and potential strategies to amplify delivery efficiency are also discussed.
EXPERT OPINION ON DRUG DELIVERY
(2023)
Letter
Cardiac & Cardiovascular Systems
Jing-Zhang Wang, Wen-Tao Du, Gui-Jing Liu
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2017)
Review
Immunology
Jing-Zhang Wang, Wen-Tao Du, Yan-Li Xu, Shu-Zhen Cheng, Zhi-Jun Liu
MICROBIAL PATHOGENESIS
(2017)
Letter
Clinical Neurology
Jing-Zhang Wang, Jing Bai
JOURNAL OF CLINICAL NEUROSCIENCE
(2018)
Letter
Cardiac & Cardiovascular Systems
Jing-Zhang Wang
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2018)
Article
Neurosciences
Jing-Zhang Wang, Wen-Tao Du, Jing Bai, Shu-Zhen Cheng, Yu-Hua Zhang
JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
(2020)