Pulmonary surfactant and COVID-19: A new synthesis

Chapter 1: COVID-19 pathogenesis poses paradoxes difficult to explain with traditional physiology. For instance, since type II pneumocytes are considered the primary cellular target of SARS-CoV-2;as these produce pulmonary surfactant (PS), the possibility that insufficient PS plays a role in COVID-19 pathogenesis has been raised. However, the opposite of predicted high alveolar surface tension is found in many early COVID-19 patients: paradoxically normal lung volumes and high compliance occur, with profound hypoxemia. That 'COVID anomaly' was quickly rationalised by invoking traditional vascular mechanisms-mainly because of surprisingly preserved alveolar surface in early hypoxemic cases. However, that quick rejection of alveolar damage only occurred because the actual mechanism of gas exchange has long been presumed to be non-problematic, due to diffusion through the alveolar surface. On the contrary, we provide physical chemical evidence that gas exchange occurs by an process of expansion and contraction of the three-dimensional structures of PS and its associated proteins. This view explains anomalous observations from the level of cryo-TEM to whole individuals. It encompasses results from premature infants to the deepest diving seals. Once understood, the COVID anomaly dissolves and is straightforwardly explained as covert viral damage to the 3D structure of PS, with direct treatment implications. As a natural experiment, the SARS-CoV-2 virus itself has helped us to simplify and clarify not only the nature of dyspnea and its relationship to pulmonary compliance, but also the fine detail of the PS including such features as water channels which had heretofore been entirely unexpected.Copyright ©

Oxygen therapy alternatives in COVID-19: From classical to nanomedicine.

Around 10-15% of COVID-19 patients affected by the Delta and the Omicron variants exhibit acute respiratory insufficiency and require intensive care unit admission to receive advanced respiratory support. However, the current ventilation methods display several limitations, including lung injury, dysphagia, respiratory muscle atrophy, and hemorrhage. Furthermore, most of the ventilatory techniques currently offered require highly trained professionals and oxygen cylinders, which may attain short supply owing to the high demand and misuse. Therefore, the search for new alternatives for oxygen therapeutics has become extremely important for maintaining gas exchange in patients affected by COVID-19. This review highlights and suggest new alternatives based on micro and nanostructures capable of supplying oxygen and/or enabling hematosis during moderate or acute COVID-19 cases.

A microfluidic device for real-time on-demand intravenous oxygen delivery.

SignificanceThe treatment of hypoxemia that is refractory to the current standard of care is time-sensitive and requires skilled caregivers and use of specialized equipment (e.g., extracorporeal membrane oxygenation). Most patients experiencing refractory hypoxemia will suffer organ dysfunction, and death is common in this cohort. Here, we describe a new strategy to stabilize and support patients using a microfluidic device that administers oxygen gas directly to the bloodstream in real time and on demand using a process that we call sequential shear-induced bubble breakup. If successful, the described technology may help to avoid or decrease the incidence of ventilator-related lung injury from refractory hypoxemia.

Targeted Nanobubble Technology to Control Diabetic Macrophage Function

Purpose and Scope. The use of micro- and nanobubble systems combined with ultrasound (US) for drug and gene delivery hasgained attention because the US can be used to trigger and enhance delivery via sonoporation. The objective of the proposedresearch is to develop a novel approach of miR-21 mimic cargo delivery using targeted gas nonobubbles. The delivery isanticipated to improve plasticity of injury-site macrophages in diabetic ulcers thus, facilitating resolution of inflammation andpromote wound healing. Results and Significance. I) Successfully formulated macrophage targeted cationic nanobubbles (mNB)which are sufficiently stable to allow for adequate therapy time. II) optimized the delivery of mNB in excisional wounds that wastrackable under US imaging using Vevo2100. In preliminary experiments, the delivery resulted in improved wound closure in adelayed wound healing mice model of miR-21lysM cre.

Developing Actively Targeted Nanoparticles to Fight Cancer: Focus on Italian Research.

Active targeting is a valuable and promising approach with which to enhance the therapeutic efficacy of nanodelivery systems, and the development of tumor-targeted nanoparticles has therefore attracted much research attention. In this field, the research carried out in Italian Pharmaceutical Technology academic groups has been focused on the development of actively targeted nanosystems using a multidisciplinary approach. To highlight these efforts, this review reports a thorough description of the last 10 years of Italian research results on the development of actively targeted nanoparticles to direct drugs towards different receptors that are overexpressed on cancer cells or in the tumor microenvironment. In particular, the review discusses polymeric nanocarriers, liposomes, lipoplexes, niosomes, solid lipid nanoparticles, squalene nanoassemblies and nanobubbles. For each nanocarrier, the main ligands, conjugation strategies and target receptors are described. The literature indicates that polymeric nanoparticles and liposomes stand out as key tools for improving specific drug delivery to the site of action. In addition, solid lipid nanoparticles, squalene nanoparticles and nanobubbles have also been successfully proposed. Taken together, these strategies all offer many platforms for the design of nanocarriers that are suitable for future clinical translation.