Advanced Nitric Oxide Generating Nanomedicine for Therapeutic Applications.

Nitric oxide (NO), a gaseous transmitter extensively present in the human body, regulates vascular relaxation, immune response, inflammation, neurotransmission, and other crucial functions. Nitrite donors have been used clinically to treat angina, heart failure, pulmonary hypertension, and erectile dysfunction. Based on NO's vast biological functions, it further can treat tumors, bacteria/biofilms and other infections, wound healing, eye diseases, and osteoporosis. However, delivering NO is challenging due to uncontrolled blood circulation release and a half-life of under five seconds. With advanced biotechnology and the development of nanomedicine, NO donors packaged with multifunctional nanocarriers by physically embedding or chemically conjugating have been reported to show improved therapeutic efficacy and reduced side effects. Herein, we review and discuss recent applications of NO nanomedicines, their therapeutic mechanisms, and the challenges of NO nanomedicines for future scientific studies and clinical applications. As NO enables the inhibition of the replication of DNA and RNA in infectious microbes, including COVID-19 coronaviruses and malaria parasites, we highlight the potential of NO nanomedicines for antipandemic efforts. This review aims to provide deep insights and practical hints into design strategies and applications of NO nanomedicines.

Spotlight on Genetic Kidney Diseases: A Call for Drug Delivery and Nanomedicine Solutions.

Nanoparticles as drug delivery carriers have benefited diseases, including cancer, since the 1990s, and more recently, their promise to quickly and efficiently be mobilized to fight against global diseases such as in the COVID-19 pandemic have been proven. Despite these success stories, there are limited nanomedicine efforts for chronic kidney diseases (CKDs), which affect 844 million people worldwide and can be linked to a variety of genetic kidney diseases. In this Perspective, we provide a brief overview of the clinical status of genetic kidney diseases, background on kidney physiology and a summary of nanoparticle design that enable kidney access and targeting, and emerging technological strategies that can be applied for genetic kidney diseases, including rare and congenital kidney diseases. Finally, we conclude by discussing gaps in knowledge remaining in both genetic kidney diseases and kidney nanomedicine and collective efforts that are needed to bring together stakeholders from diverse expertise and industries to enable the development of the most relevant drug delivery strategies that can make an impact in the clinic.

Targeting vascular inflammation through emerging methods and drug carriers.

Acute inflammation is a common dangerous component of pathogenesis of many prevalent conditions with high morbidity and mortality including sepsis, thrombosis, acute respiratory distress syndrome (ARDS), COVID-19, myocardial and cerebral ischemia-reperfusion, infection, and trauma. Inflammatory changes of the vasculature and blood mediate the course and outcome of the pathology in the tissue site of insult, remote organs and systemically. Endothelial cells lining the luminal surface of the vasculature play the key regulatory functions in the body, distinct under normal vs. pathological conditions. In theory, pharmacological interventions in the endothelial cells might enable therapeutic correction of the overzealous damaging pro-inflammatory and pro-thrombotic changes in the vasculature. However, current agents and drug delivery systems (DDS) have inadequate pharmacokinetics and lack the spatiotemporal precision of vascular delivery in the context of acute inflammation. To attain this level of precision, many groups design DDS targeted to specific endothelial surface determinants. These DDS are able to provide specificity for desired tissues, organs, cells, and sub-cellular compartments needed for a particular intervention. We provide a brief overview of endothelial determinants, design of DDS targeted to these molecules, their performance in experimental models with focus on animal studies and appraisal of emerging new approaches. Particular attention is paid to challenges and perspectives of targeted therapeutics and nanomedicine for advanced management of acute inflammation.

Diverse Effects of Exosomes on COVID-19: A Perspective of Progress From Transmission to Therapeutic Developments.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus and the causative agent of the current global pandemic of coronavirus disease 2019 (COVID-19). There are currently no FDA-approved antiviral drugs for COVID-19 and there is an urgent need to develop treatment strategies that can effectively suppress SARS-CoV-2 infection. Numerous approaches have been researched so far, with one of them being the emerging exosome-based therapies. Exosomes are nano-sized, lipid bilayer-enclosed structures, share structural similarities with viruses secreted from all types of cells, including those lining the respiratory tract. Importantly, the interplay between exosomes and viruses could be potentially exploited for antiviral drug and vaccine development. Exosomes are produced by virus-infected cells and play crucial roles in mediating communication between infected and uninfected cells. SARS-CoV-2 modulates the production and composition of exosomes, and can exploit exosome formation, secretion, and release pathways to promote infection, transmission, and intercellular spread. Exosomes have been exploited for therapeutic benefits in patients afflicted with various diseases including COVID-19. Furthermore, the administration of exosomes loaded with immunomodulatory cargo in combination with antiviral drugs represents a novel intervention for the treatment of diseases such as COVID-19. In particular, exosomes derived from mesenchymal stem cells (MSCs) are used as cell-free therapeutic agents. Mesenchymal stem cell derived exosomes reduces the cytokine storm and reverse the inhibition of host anti-viral defenses associated with COVID-19 and also enhances mitochondrial function repair lung injuries. We discuss the role of exosomes in relation to transmission, infection, diagnosis, treatment, therapeutics, drug delivery, and vaccines, and present some future perspectives regarding their use for combating COVID-19.

Role of chitosan based nanomedicines in the treatment of chronic respiratory diseases.

Chitosan-loaded nanomedicines provide a greater opportunity for the treatment of respiratory diseases. Natural biopolymer chitosan and its derivatives have a large number of proven pharmacological actions like antioxidant, wound healing, immuno-stimulant, hypocholesterolemic, antimicrobial, obesity treatment, anti-inflammatory, anticancer, bone tissue engineering, antifungal, regenerative medicine, anti-diabetic and mucosal adjuvant, etc. which attracted its use in the pharmaceutical industry. As compared to other polysaccharides, chitosan has excellent mucoadhesive characteristics, less viscous, easily modified into the chemical and biological molecule and gel-forming property due to which the drugs retain in the respiratory tract for a longer period of time providing enhanced therapeutic action of the drug. Chitosan-based nanomedicines would have the greatest effect when used to transport poor water soluble drugs, macromolecules like proteins, and peptides through the lungs. In this review, we highlight and discuss the role of chitosan and its nanomedicines in the treatment of chronic respiratory diseases such as pneumonia, asthma, COPD, lung cancer, tuberculosis, and COVID-19.