Evaluation of intranasal delivery route of drug administration for brain targeting

Publisher's version (útgefin grein)The acute or chronic drug treatments for different neurodegenerative and psychiatric disorders are challengingfrom several aspects. The low bioavailability and limited brain exposure of oral drugs, the rapid metabolism,elimination, the unwanted side effects and also the high dose to be added mean both inconvenience for thepatients and high costs for the patients, their family and the society. The reason of low brain penetration of thecompounds is that they have to overcome the blood-brain barrier which protects the brain against xenobiotics.Intranasal drug administration is one of the promising options to bypass blood-brain barrier, to reduce thesystemic adverse effects of the drugs and to lower the doses to be administered. Furthermore, the drugs ad-ministered using nasal route have usually higher bioavailability, less side effects and result in higher brainexposure at similar dosage than the oral drugs. In this review the focus is on giving an overview on the ana-tomical and cellular structure of nasal cavity and absorption surface. It presents some possibilities to enhance thedrug penetration through the nasal barrier and summarizes somein vitro,ex vivoandin vivotechnologies to testthe drug delivery across the nasal epithelium into the brain. Finally, the authors give a critical evaluation of thenasal route of administration showing its main advantages and limitations of this delivery route for CNS drugtargetingThe authors thank the Faculty of Information Technology andBionics, Pázmány Péter Catholic University, Budapest, for the supportof the publication costs of this article. This work was partly supportedby the European Union through grant no. EFOP-3.6.3-VEKOP-16-2017-00002 co-financed by the European Social Fund and also by theNational Bionics Program of Hungary.Peer Reviewe

SARS-CoV-2 infection in cardiovascular disease: Unmet need of stem cell models

This review aims to summarise new approaches in SARS-CoV-2-related research in cardiology. We provide a head-to-head comparison of models, such as animal research and human pluripotent stem cells, to investigate the pathomechanisms of COVID-19 and find an efficient therapy. In vivo methods were useful for studying systemic processes of the disease; however, due to differences in animal and human biology, the clinical translation of the results remains a complex task. In vitro stem cell research makes cellular events more observable and effective for finding new drugs and therapies for COVID-19, including the use of stem cells. Furthermore, multicellular 3D organoids even make it possible to observe the effects of drugs to treat SARS-CoV-2 infection in human organ models

Overcoming the Blood–Brain Barrier. Challenges and Tricks for CNS Drug Delivery

Treatment of certain central nervous system disorders, including different types of cerebral malignancies, is limited by traditional oral or systemic administrations of therapeutic drugs due to possible serious side effects and/or lack of the brain penetration and, therefore, the efficacy of the drugs is diminished. During the last decade, several new technologies were developed to overcome barrier properties of cerebral capillaries. This review gives a short overview of the structural elements and anatomical features of the blood⁻brain barrier. The various in vitro (static and dynamic), in vivo (microdialysis), and in situ (brain perfusion) blood⁻brain barrier models are also presented. The drug formulations and administration options to deliver molecules effectively to the central nervous system (CNS) are presented. Nanocarriers, nanoparticles (lipid, polymeric, magnetic, gold, and carbon based nanoparticles, dendrimers, etc.), viral and peptid vectors and shuttles, sonoporation and microbubbles are briefly shown. The modulation of receptors and efflux transporters in the cell membrane can also be an effective approach to enhance brain exposure to therapeutic compounds. Intranasal administration is a noninvasive delivery route to bypass the blood⁻brain barrier, while direct brain administration is an invasive mode to target the brain region with therapeutic drug concentrations locally. Nowadays, both technological and mechanistic tools are available to assist in overcoming the blood⁻brain barrier. With these techniques more effective and even safer drugs can be developed for the treatment of devastating brain disorders

Development of Skin-On-A-Chip Platforms for Different Utilizations: Factors to Be Considered

There is increasing interest in miniaturized technologies in diagnostics, therapeutic testing, and biomedicinal fundamental research. The same is true for the dermal studies in topical drug development, dermatological disease pathology testing, and cosmetic science. This review aims to collect the recent scientific literature and knowledge about the application of skin-on-a-chip technology in drug diffusion studies, in pharmacological and toxicological experiments, in wound healing, and in fields of cosmetic science (ageing or repair). The basic mathematical models are also presented in the article to predict physical phenomena, such as fluid movement, drug diffusion, and heat transfer taking place across the dermal layers in the chip using Computational Fluid Dynamics techniques. Soon, it can be envisioned that animal studies might be at least in part replaced with skin-on-a-chip technology leading to more reliable results close to study on humans. The new technology is a cost-effective alternative to traditional methods used in research institutes, university labs, and industry. With this article, the authors would like to call attention to a new investigational family of platforms to refresh the researchers’ theranostics and preclinical, experimental toolbox