Potential application of injectable chitosan hydrogel treated with siRNA in chronic rhinosinusitis therapy

Chronic rhinosinusitis is a condition with severe clinical symptoms and limited therapeutic solutions. It has been reported that vascular endothelial growth factor (VEGF) can promote nasal epithelial cell growth and result in hyperplasia of the sinuses. Therefore, the downregulation of VEGF may inhibit the process of hyperplasia. In the present study, small interfering RNA (siRNA) targeting VEGF was used to silence the expression of VEGF, and injectable chitosan based hydrogel, which is suitable for sinus injection and exhibits long-term retention, was prepared as the siRNA carrier. Human bronchial epithelial cells were cultured directly on the hydrogel to observe the biological performance in vitro. Further in vivo effects were investigated by the injection of the hydrogel into the sinus cavity. Following the introduction of siRNA introducing, the expression of VEGF in the bronchial epithelial cells was significantly suppressed at mRNA and protein levels. The number of living cells on the gel was significantly decreased, thus resulting in the inhibition of proliferation. However, the cytoskeletal arrangement of the remaining cells were not affected substantially. The hydrogel was able to retain the siRNA for an extended duration, which enabled a sustained supply of siRNA. The in vivo sinus mucosa analysis revealed that the siRNA was able to collocate with cells and the mucosa thickness was substantially decreased. In conclusion, the results of the present study suggested that injectable chitosan based hydrogel, treated with siRNA targeting VEGF, may be used as a convenient therapeutic option for chronic rhinosinusitis.