# Steering the Clinical Translation of Delivery Systems for Drugs and Health Products
## 3 Poster Presentations
### Localized Treatment of Nasal Wounds Using a Thermosensitive Chitosan-Based Nasal Spray  
[PERSON] 1,2 [PERSON] 2,3, [PERSON] 2, [PERSON] 1, [PERSON] 2, [PERSON] 2, [PERSON] 4, [PERSON] 3 and [PERSON] 2  
1 School of Engineering, Macquarie University, Sydney NSW 2109, Australia  
2 Respiratory Technology, Woolcock Institute of Medical Research, Discipline of Pharmacology, Faculty of Medicine and Health, Sydney NSW 2050, Australia  
3 Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy  
4 School of Aerospace, Mechanical and Mechatronic Engineering, The University of Sydney, Sydney NSW 2006, Australia  
* Correspondence: [EMAIL_ADDRESS]  
Loss of integrity of nasal mucosa may be accompanied by in nose bleeding (epistaxis), which may require medical intervention to control hemorrhage [59]. Available medications may cause discomfort and complications [60].  
The aim of the work was to prepare a nasal spray formulation endowed with in situ gelling properties. A thermosensitive nasal formulation based on chitosan (CS), and \(\beta\)-glycerophosphate (GP) salt, was prepared (by mixing the CS and CP solutions in an optimized volume ratio) and loaded with tranexamic acid (TXA), one of the most effective pharmacological tools to control bleeding, at different concentrations [61; 62].  
The thermogelling properties, in terms of gelation time and temperature, were investigated using both the inverted test tube method and rheology. The reversibility of sol-gel transition was also assessed. The spray and aerosolization properties of the nasal formulation were investigated and characterized in terms of spray pattern (visually) nasal deposition (using a human nose model), aerodynamic particle size distribution and deposition pattern in the respiratory tract (using the USP Next Generation Impactor). The following in vitro biological tests were performed: cytotoxicity (usinga viability test on RPMI 2650 epithelial nasal cells) and wound healing properties (using a scratch assay on nasal cells on an Air Liquid Interface model). Main results are shown in Figures 17 and 18.  
The intersection between G\" and G' at 32 \({}^{\circ}\)C indicated the gelling temperature (Figure 17). The sol-gel transition was reversible until the third cycle of heating and cooling. The approximate gelation time for TXA-CS-\(\beta\)-GP with 1% w/v TXA was 5 min [63].  
The developed formulation showed no toxic effect on human nasal epithelial cells at the concentrations used and allowed faster wound gap closure as compared to the control TXA solution. The onset of wound closure was 5.94 times faster (at 1 h) after application of the formulation as compared to the control (Figure 19).  
Figure 17: Representation of gelation temperature.  
Figure 18: The gelation of the formulation (**b**) on the nasal surface (human nasal model) occurred in 5 min at 37 \({}^{\circ}\)C and stopped nasal run off, and the deposition pattern on the wall of the nasal cast cavity remained unchanged from 5 to 20 min. In contrast, control continued to show leakage (**c**). The aerodynamic particle size distribution (about 90% \(>\)10 \(\upmu\)m) was consistent with nasal deposition.  
In conclusion, the nasal spray developed showed rapid gelation in 5 min at 32 \({}^{\circ}\)C with reversible mechanism and an ideal spray and deposition pattern for nasal drug delivery. It could prevent nasal runoff and enhance residence time. It proved safe on human nasal epithelial cells and efficient in wound closure in the first 3 h.  
The support of the II level Master Course in Pharmaceutical Technology and Regulatory Affairs of Pavia University is greatly appreciated.  
The authors declare no conflict of interest. Figures 17 and 18 are modified from a related paper submitted to AAPS Pharm Tech Journal ([[http://dx.doi.org/10.1208/s12249-019-1517-6](http://dx.doi.org/10.1208/s12249-019-1517-6)]([http://dx.doi.org/10.1208/s12249-019-1517-6](http://dx.doi.org/10.1208/s12249-019-1517-6))).