School of Engineering, Macquarie University, Sydney, Australia.
Respiratory Technology, Discipline of Pharmacology, Faculty of Medicine and Health, Woolcock Institute of Medical Research, Sydney, NSW, 2037, Australia.
AAPS PharmSciTech. 2019 Sep 3;20(7):299. doi: 10.1208/s12249-019-1517-6.
The integrity of the nasal epithelium plays a crucial role in the airway defence mechanism. The nasal epithelium may be injured as a result of a large number of factors leading to nose bleeds, also known as epistaxis. However, local measures commonly used to treat epistaxis and improve wound healing present several side effects and patient discomfort. Hence, this study aims to address some of these drawbacks by developing a new formulation for nasal epithelial wound healing. Chitosan, a biodegradable and biocompatible polymer, was used to develop a thermosensitive nasal formulation for the delivery of tranexamic acid (TXA), one of the most effective pharmacological options to control bleeding with cost and tolerability advantages. The in situ gelation properties of the formulation upon administration in the nasal cavity were investigated in terms of gelation time and temperature. It was found that the developed formulation can undergo rapid liquid-to-gel phase change within approximately 5 min at 32°C, which is well within the human nasal cavity temperature range. The spray pattern, deposition and droplet size generated by the nasal spray was also characterised and were found to be suitable for nasal drug delivery. It was also observed that the in situ gelation of the formulation prevent nasal runoff, while the majority of drug deposited mainly in the anterior part of the nose with no lung deposition. The developed formulation was shown to be safe on human nasal epithelium and demonstrated six times faster wound closure compared to the control TXA solution.
鼻腔上皮的完整性在气道防御机制中起着至关重要的作用。由于许多因素会导致鼻出血（即鼻衄），从而损伤鼻腔上皮。然而，临床上常用于治疗鼻衄和促进伤口愈合的局部措施存在一些副作用和患者不适。因此，本研究旨在通过开发一种新的鼻腔上皮伤口愈合制剂来解决其中的一些缺陷。壳聚糖是一种可生物降解和生物相容的聚合物，用于开发一种用于传递氨甲环酸（TXA）的温敏性鼻腔制剂，TXA 是控制出血最有效的药理学选择之一，具有成本和耐受性优势。该制剂在鼻腔内给药时的原位凝胶形成特性，包括凝胶时间和温度，进行了研究。结果发现，该制剂在 32°C 下约 5 分钟内即可迅速发生从液态到凝胶的相转变，这在人体鼻腔温度范围内。还对鼻腔喷雾产生的喷雾模式、沉积和液滴大小进行了表征，结果表明它们适用于鼻腔给药。此外，还观察到该制剂的原位凝胶化可以防止鼻漏，而大部分药物主要沉积在鼻子的前部，没有肺部沉积。该制剂在人鼻腔上皮组织上表现出安全性，并且与对照 TXA 溶液相比，其伤口闭合速度快了六倍。
