Studies of Mucosal Irritation and Cellular Uptake Mechanisms of Xingnaojing Nanoemulsion

Abstract Xingnaojing (XNJ) injection was used to treat pneumonia and stroke in clinic in China, but with poor patient compliance. Xingnaojing nanoemulsion for intranasal delivery was developed to improve it. This article tried to evaluate the mucosal irritation of Xingnaojing nanoemulsion and investigate cellular uptake mechanism of its encapsulated lipophilic drugs. The toad palate model and rat nasal mucosa model were used to study the nasal ciliotoxicity and nasal mucosal irritation of nanoemulsion to evaluate its safety intranasally. The cellular uptake mechanism was studied by Calu-3 cell model. Coumarin 6 was encapsulated in nanoemulsion and the endocytic pathways were studied by cellular uptake experiments after being treated with different inhibitors. In toad palate model, the cilia movement of Xingnaojing nanoemulsion group last for 467.40 ± 39.02 min, which was obviously longer than deoxycholate group (90.60 ± 15.40 min). Studies on rats showed that the damage caused by nanemulsion is capable of being recovered. Nanoemulsion uptake was reduced obviously when cells were treated with wortmannin, and it also decreased about 13% when the temperature reduced from 37ºC to 4ºC. Mucosal irritation caused by nanoemulsion is low and the damage is recoverable. The cellular uptake of Xingnaojing nanoemulsion is energy-dependent, and macropinocytosis was the most important pathway for cellular uptake.

Diagnosis of adult chronic rhinosinusitis: can nasal endoscopy predict intrasinus disease?

To define the role of endoscopic evaluation of middle meatus in adult patients clinically diagnosed to have chronic rhinosinusitis and its ability to predict intra-sinus mucosal involvement as compared to CT scan. This prospective analytical study was conducted on consecutive patients with diagnosis of chronic rhino-sinusitis who were symptomatic and fulfilled the American Academy of Otolaryngology - Head and Neck Surgery Task Force criteria. The patients were enrolled prospectively and were subjected to rigid diagnostic nasal endoscopy and classified as defined by the revised Sinus Allergy Health Partnership Task Force criteria. The patients then underwent non contrast CT sinuses on the same day. Results were analyzed as a diagnostic test evaluation using CT as a gold standard. Among the 75 study patients with symptom based chronic rhino-sinusitis, nasal endoscopy was abnormal in 65 patients [87%]. Of these patients, 60/65 [92%] showed positive findings on CT scan. Ten patients had normal endoscopy, of these 6/10 [60%] had abnormal CT scan. Sensitivity and specificity of diagnostic nasal endoscopy against CT scan were 91% [95% CI: 81-97] and 44% [95% CI: 14-79], respectively. The likelihood ratio for positive nasal endoscopy to diagnose chronic rhino-sinusitis was 1.6 and the likelihood ratio to rule out chronic rhino-sinusitis when endoscopy was negative was 0.2. Nasal endoscopy is a valid and objective diagnostic tool in the work up of patients with symptomatic chronic rhinosinusitis. When clinical suspicion is low [<50%] and endoscopy is negative, the probability of rhino-sinusitis is very low [<17%] and there is no need to perform a CT scan to reconfirm this finding routinely. Endoscopy alone is able to diagnose chronic rhinosinusitis in >90% of patients when clinical suspicion is high [88%] as defined in this study by AAO-HNS Task Force criteria. Negative endoscopy, however, does not totally exclude the sinus disease in patients fulfilling task force criteria. CT scan may be needed on follow-up if there is clinical suspicion in 10% of these patients who are negative on endoscopy if symptoms persists. It is thus possible to reduce the number of CT scans if patients are carefully selected based on clinical criteria and endoscopy is done initially as part of their evaluation.