Mucoadhesive drug delivery systems: a promising noninvasive approach to bioavailability enhancement. Part II: formulation considerations.

INTRODUCTION: Mucoadhesive drug delivery systems (MDDS) are specifically designed to interact and bind to the mucosal layer of the epithelium for localized, prolonged, and/or targeted drug delivery. Over the past 4 decades, several dosage forms have been developed for localized as well as systemic drug delivery at different anatomical sites. AREAS COVERED: The objective of this review is to provide a detailed understanding of the different aspects of MDDS. Part II describes the origin and evolution of MDDS, followed by a discussion of the properties of mucoadhesive polymers. Finally, a synopsis of the different commercial aspects of MDDS, recent advances in the development of MDDS for biologics and COVID-19 as well as future perspectives are provided. EXPERT OPINION: A review of the past reports and recent advances reveal MDDS as highly versatile, biocompatible, and noninvasive drug delivery systems. The rise in the number of approved biologics, the introduction of newer highly efficient thiomers, as well as the recent advances in the field of nanotechnology have led to several excellent applications of MDDS, which are predicted to grow significantly in the future.

Evaluating Feasibility of Human Tissue Engineered Respiratory Epithelium Construct as a Potential Model for Tracheal Mucosal Reconstruction.

The normal function of the airway epithelium is vital for the host's well-being. Conditions that might compromise the structure and functionality of the airway epithelium include congenital tracheal anomalies, infection, trauma and post-intubation injuries. Recently, the onset of COVID-19 and its complications in managing respiratory failure further intensified the need for tracheal tissue replacement. Thus far, plenty of naturally derived, synthetic or allogeneic materials have been studied for their applicability in tracheal tissue replacement. However, a reliable tracheal replacement material is missing. Therefore, this study used a tissue engineering approach for constructing tracheal tissue. Human respiratory epithelial cells (RECs) were isolated from nasal turbinate, and the cells were incorporated into a calcium chloride-polymerized human blood plasma to form a human tissue respiratory epithelial construct (HTREC). The quality of HTREC in vitro, focusing on the cellular proliferation, differentiation and distribution of the RECs, was examined using histological, gene expression and immunocytochemical analysis. Histological analysis showed a homogenous distribution of RECs within the HTREC, with increased proliferation of the residing RECs within 4 days of investigation. Gene expression analysis revealed a significant increase (p < 0.05) in gene expression level of proliferative and respiratory epithelial-specific markers Ki67 and MUC5B, respectively, within 4 days of investigation. Immunohistochemical analysis also confirmed the expression of Ki67 and MUC5AC markers in residing RECs within the HTREC. The findings show that calcium chloride-polymerized human blood plasma is a suitable material, which supports viability, proliferation and mucin secreting phenotype of RECs, and this suggests that HTREC can be a potential candidate for respiratory epithelial tissue reconstruction.

Hypersensitivity may be involved in severe COVID-19.

BACKGROUND: Deaths attributed to Coronavirus Disease 2019 (COVID-19) are mainly due to severe hypoxemic respiratory failure. Although the inflammatory storm has been considered the main pathogenesis of severe COVID-19, hypersensitivity may be another important mechanism involved in severe cases, which have a perfect response to corticosteroids (CS). METHOD: We detected the serum level of anti-SARS-CoV-2-spike S1 protein-specific IgE (SP-IgE) and anti-SARS-CoV-2 nucleocapsid protein-specific IgE (NP-IgE) in COVID-19. Correlation of levels of specific IgE and clinical severity were analysed. Pulmonary function test and bronchial provocation test were conducted in early convalescence of COVID-19. We also obtained histological samples via endoscopy to detect the evidence of mast cell activation. RESULT: The levels of serum SP-IgE and NP-IgE were significantly higher in severe cases, and were correlated with the total lung severity scores (TLSS) and the PaO2 /FiO2 ratio. Nucleocapsid protein could be detected in both airway and intestinal tissues, which was stained positive together with activated mast cells, binded with IgE. Airway hyperresponsiveness (AHR) exists in the early convalescence of COVID-19. After the application of CS in severe COVID-19, SP-IgE and NP-IgE decreased, but maintained at a high level. CONCLUSION: Hypersensitivity may be involved in severe COVID-19.

Natural nasal-esophageal fiberscopy in the COVID-19 pandemic-preventing sneezing without anesthesia: a case report.

BACKGROUND: We are laryngologists. We observe natural phonatory and swallowing functions in clinical examinations with a trans-nasal laryngeal fiberscope (TNLF). Before each observation, we use epinephrine to enlarge and smooth the common nasal meatus (bottom of nostril) and then insert a wet swab inside the nose, as in taking a swab culture in the nasopharynx. During the current COVID-19 pandemic situation, this careful technique prevents any complications, including nasal bleeding, painfulness, and induced sneezing. Here, we introduce our routine to observe esophageal movement in swallowing in a natural (sitting) position without anesthesia. CASE PRESENTATION: The case was a 70-year-old female who complained that something was stuck in her esophagus; there was a strange sensation below the larynx and pharynx. After enlarging and smoothing the common nasal meatus, we inserted the TNLF (slim type ⌀2.9 mm fiberscope, VNL8-J10, PENTAX Medical, Tokyo, Japan.) in the normal way. We then observed the phonatory and swallowing movements of the vocal folds. As usual, to not interfere with natural movements, we used no anesthesia. We found no pathological condition in the pyriform sinus. We asked the patient to swallow the fiberscope. During the swallow, we pushed the TNLF and inserted the tip a bit deeper, which made the fiberscope easily enter the esophagus, like in the insertion of a nasogastric tube. We then asked the patient to swallow a sip of water or saliva to clear and enlarge the lumen of the esophagus. This made it possible to observe the esophagus easily without any air supply. With tone enhancement scan, the esophagus was found to be completely normal except for glycogenic acanthosis. CONCLUSIONS: The advantage of this examination is that it is easily able to perform without anesthesia and with the patient in sitting position. It is quick and minimally invasive, enabling observation the physiologically natural swallowing. It is also possible to observe without anesthesia down to the level of the esophagogastric junction using with a thin type flexible bronchoscope. In the future, gastric fiberscopes might be thinner, even with narrow band imaging (NBI) function. Before that time, physicians should remember to just insert along the bottom of the nose.

Predictive effects of IgA and IgG combination to assess pulmonary exudation progression in COVID-19 patients.

Our study intended to longitudinally explore the prediction effect of immunoglobulin A (IgA) on pulmonary exudation progression in COVID-19 patients. The serum IgA was tested with chemiluminescence method. Autoregressive moving average model was used to extrapolate the IgA levels before hospital admission. The positive rate of IgA and IgG in our cohort was 97% and 79.0%, respectively. In this study, the IgA levels peaks within 10-15 days after admission, while the IgG levels peaks at admission. We found that the time difference between their peaks was about 10 days. Viral RNA detection results showed that the positive rate in sputum and feces were the highest. Blood gas analysis showed that deterioration of hypoxia with the enlargement of pulmonary exudation area. And alveolar-arterial oxygen difference and oxygenation index were correlated with IgA and IgG. The results of biopsy showed that the epithelium of lung was exfoliated and the mucosa was edematous. In severe COVID-19 patients, the combination of IgA and IgG can predict the progress of pulmonary lesions and is closely related to hypoxemia and both also play an important defense role in invasion and destruction of bronchial and alveolar epithelium by SARS-CoV-2.