Review
Chemistry, Physical
Yue Jiang, Xueting Pan, Tao Yu, Hai Wang
Summary: The existence of the blood-brain barrier (BBB) poses challenges for drug delivery to the central nervous system (CNS). Intranasal administration has emerged as an alternative method for delivering drugs to the brain by bypassing the BBB. This review focuses on the mechanisms, properties, and strategies of intranasal nanosystems for brain-targeted drug delivery. Despite promising results in animal models and clinical applications, significant challenges need to be overcome for the translation of these nanosystems into clinics. The future prospects of intranasal drug delivery nanosystems are discussed, aiming to provide insights and guidance for effective neurological disease treatment.
Article
Pharmacology & Pharmacy
Dipy M. Vasa, Zainab Bakri, Maureen D. Donovan, Lauren A. O'Donnell, Peter L. D. Wildfong
Summary: Combining ribavirin with poloxamer 188 can enhance drug permeability across the olfactory epithelium, suggesting the potential for improved direct nose-to-brain transport.
Article
Pharmacology & Pharmacy
Bhanu Teja Surikutchi, Rebeca Obenza-Otero, Emanuele Russo, Mischa Zelzer, Irene Golan Cancela, Jose A. Costoya, Jose Crecente Campo, Maria Jose Alonso, Maria Marlow
Summary: A drug-loaded hydrogel has been developed for drug delivery into the peritoneal cavity. The hydrogel's stability and drug release properties were evaluated through in vitro and in vivo experiments. This hydrogel has potential applications as a biodegradable drug delivery system that can be implanted in the peritoneal cavity.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Review
Pharmacology & Pharmacy
Vimala N. Bharadwaj, Alexander Z. Tzabazis, Michael Klukinov, Neil A. Manering, David C. Yeomans
Summary: Chronic pain, a challenging condition in medicine, is associated with plastic changes in the nervous system. Polypeptides, highly selective molecules for nervous system receptors, have potential in pain therapeutics and have shown successful deposition in the nervous system through intranasal delivery. This non-invasive method has the potential to provide rapid and effective treatment for chronic pain.
Article
Chemistry, Multidisciplinary
Yuan Lu, Julie Tzu-Wen Wang, Na Li, Xiaoqin Zhu, Yongjun Li, Sukhi Bansal, Yonglin Wang, Khuloud T. Al-Jamal
Summary: This study developed EDV-loaded polymeric nanoparticles for nose-to-brain drug delivery, improving drug stability and bioavailability. The results showed that the nanoparticle formulation achieved higher and more sustained brain uptake of EDV compared to intravenous administration, offering hope for ALS treatment.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Biochemistry & Molecular Biology
Yaswanthi Yanamadala, Mahdi Y. Saleh, Afrika A. Williams, Yuri Lvov, Teresa A. Murray
Summary: The blood-brain barrier prevents most therapeutic drugs from entering the brain, but drugs loaded within halloysite nanotubes can overcome this barrier. Halloysite nanotubes, with their needle-like shape, were used as a nano-torpedo to deliver drugs across the blood-brain barrier when administered intranasally. By loading halloysite nanotubes with diazepam or xylazine and delivering them to mice intranasally, sedative effects were observed. This study confirms that halloysite can permeate the blood-brain barrier to deliver drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Raquel Talens-Visconti, Jesus Vicente de Julian-Ortiz, Ofelia Vila-Buso, Octavio Diez-Sales, Amparo Nacher
Summary: Alzheimer-type dementia (ATD) treatments are limited in their ability to cross the blood-brain barrier and can have adverse effects on the body. Intranasal administration provides a direct route to the brain through the nasal cavity. However, drug absorption and bioavailability can be hindered by nasal physiology, so technological strategies are needed to optimize the physicochemical properties of formulations. Among the strategies explored, lipid-based nanosystems, specifically nanostructured lipid carriers, show promise in preclinical studies with minimal toxicity and therapeutic efficacy. This review focuses on the use of nanostructured lipid carriers for intranasal administration in the treatment of ATD. Currently, no drugs for intranasal administration in ATD have received marketing approval, but three candidates (insulin, rivastigmine, and APH-1105) are being clinically investigated. Further studies with other candidates will help confirm the potential of intranasal administration in the treatment of ATD.
Article
Pharmacology & Pharmacy
Asya Petkova, Ilona Kubajewska, Alexandra Vaideanu, Andreas G. Schatzlein, Ijeoma F. Uchegbu
Summary: Gene delivery to the cerebral cortex can be achieved via intranasal administration of hyaluronidase-coated polyplexes (GCPH).
Article
Medicine, Research & Experimental
Madeleine S. A. Tan, Preeti Pandey, Rink-Jan Lohman, James R. Falconer, Dan J. Siskind, Harendra S. Parekh
Summary: This study aimed to develop and characterize a clozapine-loaded nanoemulsion sol-gel for intranasal delivery. The formulation showed desirable physicochemical properties and sustained drug release, with no severe ciliotoxicity on nasal mucosa.
MOLECULAR PHARMACEUTICS
(2022)
Review
Pharmacology & Pharmacy
Zhiyu Jin, Yu Han, Danshen Zhang, Zhongqiu Li, Yongshuai Jing, Beibei Hu, Shiguo Sun
Summary: Depression is a growing mental disease in modern society, with low cure rates and high recurrence rates. The current treatment methods, primarily drug therapy combined with psychological and physical therapy, have limitations. Intranasal administration may provide a better option for the delivery of antidepressant medication.
Article
Pharmacology & Pharmacy
Elmira A. Vasilieva, Darya A. Kuznetsova, Farida G. Valeeva, Denis M. Kuznetsov, Andrey V. Zakharov, Syumbelya K. Amerhanova, Alexandra D. Voloshina, Irina V. Zueva, Konstantin A. Petrov, Lucia Ya. Zakharova
Summary: Chitosan-decorated liposomes were developed for the intranasal delivery of a reactivator for acetylcholinesterase in the brain as a therapy for poisoning from organophosphorus compounds. The polymer modification increased the encapsulation efficiency and stability of the liposomes. In vitro and in vivo experiments demonstrated the permeability of the chitosomes and their ability to reactivate brain AChE.
Article
Nanoscience & Nanotechnology
Astrid Hyldbakk, Karianne Giller Fleten, Sofie Snipstad, Andreas K. O. Aslund, Catharina de Lange Davies, Kjersti Flatmark, Yrr Morch
Summary: Colorectal and ovarian cancers commonly spread to the peritoneum, for which treatment options are limited. This study investigated the use of nanoparticles to improve the intraperitoneal delivery of cabazitaxel taxane, leading to increased drug retention, longer residence time, and higher drug concentrations in peritoneal tumors. The encapsulation of cabazitaxel in nanoparticles improved the treatment response in in vivo models, suggesting its potential as a novel treatment for peritoneal metastases.
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Joana Gonsalves, Gilberto Alves, Carla Fonseca, Andreia Carona, Joana Bicker, Amilcar Falcao, Ana Fortuna
Summary: Lacosamide, known for its anticonvulsant properties, shows potential for increasing brain exposure and could be a valuable strategy for treating epilepsy and other neurological diseases through intranasal administration.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Immunology
Rui Tada, Haruka Yamazaki, Yuzuho Nagai, Yukino Takeda, Akihiro Ohshima, Jun Kunisawa, Yoichi Negishi
Summary: The COVID-19 pandemic caused by the highly virulent SARS-CoV-2 has had a significant impact on global society. Mucosal vaccines, which can induce immune responses at both mucosal and systemic sites, could be a potential approach to combat infectious diseases. This study demonstrated that intranasal administration of the nitric oxide donor SNP had potent mucosal adjuvant effects in mice.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Barbara Sanchez-Dengra, Maria Alfonso, Isabel Gonzalez-Alvarez, Marival Bermejo, Marta Gonzalez-Alvarez, Ramon Martinez-Manez
Summary: The two types of nanoparticles loaded with ponatinib have been proven to be non-toxic to blood-brain barrier cells and have shown improved drug delivery to the brain compared to the free drug when administered intranasally. This research is significant for the treatment of brain cancer.
Review
Cardiac & Cardiovascular Systems
Lisa M. Becker, Shiau-Haln Chen, Julie Rodor, Laura P. M. H. de Rooij, Andrew H. Baker, Peter Carmeliet
Summary: Endothelial cells play a crucial role in the human body but their heterogeneity poses challenges in therapy. Recent studies have revealed the diverse functions of endothelial cells and their roles in diseases, and proposed strategies to deal with this heterogeneity.
CARDIOVASCULAR RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Jacek Kwiecinski, Evangelos Tzolos, Alexander J. Fletcher, Jennifer Nash, Mohammed N. Meah, Sebastien Cadet, Philip D. Adamson, Kajetan Grodecki, Nikhil Joshi, Michelle C. Williams, Edwin J. R. van Beek, Chi Lai, Adriana A. S. Tavares, Mark G. MacAskill, Damini Dey, Andrew H. Baker, Jonathon Leipsic, Daniel S. Berman, Stephanie L. Sellers, David E. Newby, Marc R. Dweck, Piotr J. Slomka
Summary: This study aimed to investigate the potential of F-18-sodium fluoride (F-18-NaF) positron emission tomography (PET) in identifying graft vasculopathy and to examine the impact of coronary artery bypass graft (CABG) surgery on the activity and progression of native coronary artery disease.
JACC-CARDIOVASCULAR IMAGING
(2022)
Article
Cardiac & Cardiovascular Systems
Ian R. McCracken, Ross Dobie, Matthew Bennett, Rainha Passi, Abdelaziz Beqqali, Neil C. Henderson, Joanne C. Mountford, Paul R. Riley, Chris P. Ponting, Nicola Smart, Mairi Brittan, Andrew H. Baker
Summary: The study aims to characterize the transcriptome of human foetal cardiac endothelium using single-cell RNA sequencing (scRNA-seq) to provide insights into cellular heterogeneity and transcriptional dynamics underlying endothelial specification. Results reveal distinct endothelial cell populations, endocardial contribution to coronary vasculature, and arterial specification of capillary endothelium. Transcriptional signatures defining endothelial subpopulations are largely conserved between human and mouse, with MECOM playing a role in maintaining arterial endothelial identity.
CARDIOVASCULAR RESEARCH
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
Monika M. Gladka, Andrew H. Baker
CARDIOVASCULAR RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Anda Bularga, John Hung, Marwa Daghem, Stacey Stewart, Caelan Taggart, Ryan Wereski, Trisha Singh, Mohammed N. Meah, Takeshi Fujisawa, Amy V. Ferry, Justin Chiong, William S. Jenkins, Fiona E. Strachan, Scott Semple, Edwin J. R. van Beek, Michelle Williams, Damini Dey, Chris Tuck, Andrew H. Baker, David E. Newby, Marc R. Dweck, Nicholas L. Mills, Andrew R. Chapman
Summary: Coronary and cardiac imaging of patients with type 2 myocardial infarction identified coronary artery disease in two-thirds of patients and left ventricular systolic dysfunction in one-third of patients. Unrecognized and untreated coronary or cardiac disease is seen in most patients with type 2 myocardial infarction, presenting opportunities for initiation of evidence-based treatments with major potential to improve clinical outcomes.
Article
Multidisciplinary Sciences
Julio Madrigal-Matute, Jenny de Bruijn, Kim van Kuijk, Dario F. Riascos-Bernal, Antonio Diaz, Inmaculada Tasset, Adrian Martin-Segura, Marion J. J. Gijbels, Bianca Sander, Susmita Kaushik, Erik A. L. Biessen, Simoni Tiano, Mathieu Bourdenx, Gregory J. Krause, Ian McCracken, Andrew H. Baker, Han Jin, Nicholas E. S. Sibinga, Jose Javier Bravo-Cordero, Fernando Macian, Rajat Singh, Patrick C. N. Rensen, Jimmy F. P. Berbee, Gerard Pasterkamp, Judith C. Sluimer, Ana Maria Cuervo
Summary: The study found that reduced activity of chaperone-mediated autophagy (CMA) exacerbates the progression of atherosclerosis. Conversely, up-regulated CMA in a genetic mouse model leads to lower vulnerability to atherosclerotic challenges. Thus, CMA could be an attractive therapeutic target against cardiovascular diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cardiac & Cardiovascular Systems
Ziwen Li, Emmanouil G. Solomonidis, Bronwyn Berkeley, Michelle Nga Huen Tang, Katherine Ross Stewart, Daniel Perez-Vicencio, Ian R. McCracken, Ana Mishel Spiroski, Gillian A. Gray, Anna K. Barton, Stephanie L. Sellers, Paul R. Riley, Andrew H. Baker, Mairi Brittan
Summary: We present a high-resolution single-cell meta-atlas of healthy and injured coronary endothelial cells in the mouse and human heart, revealing a suite of novel targets with great potential to promote vascular regeneration, and providing a rich resource for therapeutic development.
CARDIOVASCULAR RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Trisha Singh, Shruti Joshi, Lucy E. Kershaw, Andy H. Baker, Gerry P. McCann, Dana K. Dawson, Marc R. Dweck, Scott I. Semple, David E. Newby
Summary: Patients with takotsubo syndrome exhibit significant myocardial manganese uptake abnormality, most pronounced in the acute phase but persisting for at least 3 months despite apparent restoration of normal left ventricular ejection fraction.
Article
Cardiac & Cardiovascular Systems
Kim van Kuijk, Ian R. McCracken, Renee J. H. A. Tillie, Sebastiaan E. J. Asselberghs, Dlzar A. Kheder, Stan Muitjens, Han Jin, Richard S. Taylor, Ruud Wichers Schreur, Christoph Kuppe, Ross Dobie, Prakesh Ramachandran, Marion J. Gijbels, Lieve Temmerman, Phoebe M. Kirkwoord, Joris Luyten, Yanming Li, Heidi Noels, Pieter Goossens, John R. Wilson-Kanamori, Leon J. Schurgers, Ying H. Shen, Barend M. E. Mees, Erik A. L. Biessen, Neil C. Henderson, Rafael Kramann, Andrew H. Baker, Judith C. Sluimer
Summary: This study established specific markers for adventitial fibroblasts and analyzed their heterogeneity in response to cardiovascular diseases and risk factors. The findings revealed the functional diversity and gene expression differences among different fibroblast clusters, which are associated with cardiovascular diseases. Therefore, this study is important for understanding cardiovascular diseases and developing targeted therapies.
CARDIOVASCULAR RESEARCH
(2023)
Letter
Cardiac & Cardiovascular Systems
Julie Rodor, Shiau-Haln Chen, Andrew H. Baker
CARDIOVASCULAR RESEARCH
(2023)
Article
Multidisciplinary Sciences
T. Singh, S. Joshi, M. N. Meah, N. B. Spath, G. Papanastasiou, L. E. Kershaw, A. H. Baker, M. R. Dweck, D. E. Newby, S. I. Semple
Summary: Manganese-enhanced magnetic resonance imaging can serve as a surrogate measure for myocardial calcium handling. The repeatability and reproducibility of this imaging method have been investigated in a study involving 68 participants. The results demonstrate excellent repeatability and reproducibility in healthy myocardium, but slightly lower consistency in patients with dilated cardiomyopathy.
SCIENTIFIC REPORTS
(2023)
Article
Medicine, Research & Experimental
Valda Pauzuolyte, Aara Patel, James R. Wawrzynski, Neil J. Ingham, Yeh Chwan Leong, Rajvinder Karda, Maria Bitner-Glindzicz, Wolfgang Berger, Simon N. Waddington, Karen P. Steel, Jane C. Sowden
Summary: Deafness affects 5% of the world's population, but there is a lack of treatments for genetic hearing loss. Research using a Norrie disease mouse model and gene therapy showed that early intervention can prevent death of sensory cochlear hair cells and improve auditory function, as well as restore abnormal retinal vascularization. This has important implications for developing treatments for progressive hearing loss.
EMBO MOLECULAR MEDICINE
(2023)
Review
Endocrinology & Metabolism
Simon N. Waddington, William H. Peranteau, Ahad A. Rahim, Ashley K. Boyle, Manju A. Kurian, Paul Gissen, Jerry K. Y. Chan, Anna L. David
Summary: Fetal gene therapy was proposed in the late 1990s when gene therapy was at its peak of inflated expectations. Over the years, gene therapy matured and became a clinical and market reality. The trajectory of treatment for genetic diseases is now focused on earlier intervention, with increasing ability to diagnose genetic diseases in utero. Recent clinical trials have pointed towards the potential for fetal gene therapy. This review summarizes the history of fetal gene therapy, advancements in fetal surgery and diagnosis, and the scope of preclinical gene therapy for inherited metabolic diseases.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Review
Cell Biology
Joanne Ng, Serena Barral, Simon N. Waddington, Manju A. Kurian
Summary: Infantile parkinsonism-dystonia due to dopamine transporter deficiency syndrome (DTDS) is an ultrarare childhood movement disorder caused by biallelic loss-of-function mutations in the SLC6A3 gene. Advances in genomic analysis have revealed an evolving spectrum of SLC6A3-related neurological and neuropsychiatric disorders. In this review, we provide an overview of the expanding clinical phenotype of DTDS and the precision therapies in development, including pharmacochaperones and gene therapy.
Article
Cardiac & Cardiovascular Systems
Frederike Boos, James A. Oo, Timothy Warwick, Stefan Guenther, Judit Izquierdo Ponce, Melina Lopez, Diba Rafii, Giulia Buchmann, Minh Duc Pham, Zahraa S. Msheik, Tianfu Li, Sandra Seredinski, Shaza Haydar, Sepide Kashefiolasl, Karl H. Plate, Ruediger Behr, Matthias Mietsch, Jaya Krishnan, Soni S. Pullamsetti, Sofia-Iris Bibli, Rabea Hinkel, Andrew H. Baker, Reinier A. Boon, Marcel H. Schulz, Ilka Wittig, Francis J. Miller, Ralf P. Brandes, Matthias S. Leisegang
Summary: Long non-coding RNA LINC00607 is highly enriched in human endothelial cells and plays a regulatory role in angiogenesis by interacting with chromatin remodeler BRG1 to maintain ERG target gene transcription. Knockdown or knockout of LINC00607 attenuates VEGF-A-induced angiogenic sprouting and integration into vascular networks. Overexpression of LINC00607 restores normal endothelial function. These findings provide new insights into the role of lncRNAs in endothelial cells and their potential implications in cardiovascular disease.
BASIC RESEARCH IN CARDIOLOGY
(2023)