肉苁蓉苯乙醇苷纳米乳鼻腔给药的安全性评价

Safety evaluation of nasal delivery of Phenylethanoid Glycosides nanoemulsion

目的考察肉苁蓉苯乙醇苷纳米乳鼻腔给药的安全性。方法采用急性毒理学研究的方法将30只小鼠随机分为空白组(生理盐水)、空白制剂组(空白纳米乳)及肉苁蓉苯乙醇苷纳米乳(100mg/mL)组,各组小鼠鼻腔滴注20μL对应药物,考察经鼻给药后14d内小鼠的毒性反应情况及其生长情况;将40只小鼠随机分为空白组(生理盐水)、空白制剂组(空白纳米乳)及肉苁蓉苯乙醇苷纳米乳高(100mg/kg体质量)、低(50mg/kg体质量)剂量组,连续给药7d,每天给药1次,每次20μL,观察肉苁蓉苯乙醇苷纳米乳对小鼠行为体征的影响,记录挠鼻次数与脏器系数,通过病理组织切片考察纳米乳对小鼠鼻粘膜及心脏、肝脏等器官的影响。结果急性毒性实验小鼠经鼻给药14d后,未见毒性反应及死亡情况,与空白组相比,给药组小鼠体质量变化差异无统计学意义(P>0.05)。鼻粘膜毒性实验小鼠连续给药7d后,与空白组相比,高、低剂量给药组小鼠挠鼻次数与脏器系数变化差异无统计学意义(P>0.05)。HE图谱显示肉苁蓉苯乙醇苷纳米乳对小鼠鼻粘膜形态无影响,对小鼠心脏、肝脏及嗅球、海马等组织无影响。结论肉苁蓉苯乙醇苷纳米乳鼻腔给药无明显毒性,符合安全性要求。

Objective To investigate the safety of nasal delivery of phenylethanoid glycosides nanoemulsion. Methods Thirty mice were randomly divided into blank group （saline）, blank preparation group （blank nano-milk）, and Cistanche phenylethanide nanoemulsion group （100 mg/mL） by acute toxicology study, 20 μL of the corresponding drug was instilled, and the toxicity and growth of the mice within 14 days after nasal administration were investigated; Forty mice were randomly divided into blank group （normal saline）, blank preparation group （blank nanoemulsion）, and high dose of phenylethanoid glycosides （100 mg/kg body weight） and low （50 mg/kg body mass） dose group , continuous administration 7 days, once a day, once every 20 μL, observe the effect of Cistanche deserticola phenylethanide nanoemulsion on the behavioral signs of mice, calculate the number of snails and organ coefficient, the effects of nanoemulsion on nasal mucosa, heart and liver were observed by pathological tissue section. Results／ After 14 days of nasal administration, acute toxicity test mice showed no toxicity and death. Compared with the blank group, there was no significant difference in body weight between the mice （P 〉0.05）; after 7 days of continuous administration of nasal mucosal toxicity test mice, there was no change in the number of rhinorrhea and organ coefficient between the high and low dose groups, and the difference was not statistically significant （P 〉0.05）, HE showed that phenylethanoid glycoside nanoemulsion had no effect on the morphology of mouse nasal mucosa, and had no effect on mouse heart, liver, olfactory bulb, hippocampus and other tissues. Conclusion／ Cistanche phenylethanoid glycosides nanoemulsion nasal administration no obvious toxicity, in line with safety requirements.