Pandey Preeti, Pandey Saurabh, Cabot Peter J, Wallwork Benjamin, Panizza Benedict J, Parekh Harendra S
School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, Brisbane, Australia.
Department of Otolaryngology, Head and Neck Surgery, Princess Alexandra Hospital, Brisbane, Australia.
Saudi Pharm J. 2019 Nov;27(7):914-919. doi: 10.1016/j.jsps.2019.06.005. Epub 2019 Jun 28.
To demonstrate safety of a developed intranasal dexamethasone-infused gelling formulation, quantification of a validated clinical biomarker indicative of cytotoxic potential using a human sinonasal explant model was first confirmed. Systematic cytotoxicity studies using the lactate dehydrogenase (LDH) detection assay revealed no elevation from baseline, in LDH levels, with tissue integrity of explanted human nasal mucosa also maintained; this was further corroborated using tissue histopathological examination. Next, with safety confirmed , freshly excised human nasal tissue was utilised to quantify dexamethasone release from the lead sol-gel systems; this being achieved through development and validation of a HPLC-UV analytical method, which reliably quantified controlled therapeutic release and deposition into mucosal tissue. Collectively, these findings indicate promise in the safety of each excipient within the concentrations employed in the functional sol-gel system, complemented by successful and reliable drug release and deposition into human nasal mucosal tissue. These findings pave the way for application of the dexamethasone-based sol-gel system to the extended delivery of corticosteroids to nasal mucosa in the management of localised inflammatory conditions of an acute and chronic nature, such as chronic rhinosinusitis, which can be expected to benefit from controlled and extended drug delivery characteristics imparted by appropriately engineered gelling systems.
为了证明所开发的鼻内注入地塞米松的凝胶制剂的安全性，首先使用人鼻窦外植体模型对一种经过验证的、指示细胞毒性潜力的临床生物标志物进行了定量分析。使用乳酸脱氢酶（LDH）检测法进行的系统细胞毒性研究显示，与基线相比，LDH水平没有升高，同时移植的人鼻黏膜组织完整性也得以维持；组织组织病理学检查进一步证实了这一点。接下来，在确认安全性后，使用新鲜切除的人鼻组织来定量地塞米松从主要溶胶 - 凝胶系统中的释放；这是通过开发和验证一种高效液相色谱 - 紫外（HPLC - UV）分析方法来实现的，该方法能够可靠地定量控制治疗药物的释放以及在黏膜组织中的沉积。总体而言，这些发现表明在功能溶胶 - 凝胶系统所使用的浓度范围内，每种赋形剂都具有安全性，同时成功且可靠地将药物释放并沉积到人鼻黏膜组织中。这些发现为基于地塞米松的溶胶 - 凝胶系统在向鼻黏膜长期递送皮质类固醇以治疗急性和慢性局部炎症性疾病（如慢性鼻窦炎）方面的应用铺平了道路，预计这种疾病可受益于适当设计的凝胶系统所赋予的可控和长效药物递送特性。
