Pharmacy Discipline, School of Clinical Sciences, Queensland University of Technology, Brisbane, QLD, Australia; Institute of Health Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, QLD, Australia; Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, China.
Institute of Health Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, QLD, Australia.
Eur J Pharm Biopharm. 2020 Sep;154:175-185. doi: 10.1016/j.ejpb.2020.07.011. Epub 2020 Jul 16.
This study aimed to assess the activity of controlled release nicotine from dry powder inhaler formulation via locomotor activity of C57BL/6 mice.
To achieve this we built a nose-only inhalation device for pulmonary administration of nicotine to mice and determined the optimal operational parameters. We used the locomotor activity test to compare the effects of the inhaled nicotine hydrogen tartrate-loaded chitosan nanoparticles (NHT-CS) with NHT in C57BL/6 mice. The minimum inhaled dose of NHT-CS required to alter locomotor activity was compared with inhaled and subcutaneously (s.c) injected NHT. Finally, histological examination of lung tissues was performed to ensure inhalation of NHT-CS did not cause lung damage.
We found a flow rate of 0.9 L/min and an exposure time of 5 min achieved optimal delivery of nicotine. A minimum of 0.88 mg inhaled of NHT-CS or 0.59 mg inhaled of NHT was required to alter locomotor activity similarly to injection of 0.5 mg/kg nicotine, suggesting the reformulation process did not alter the activity of NHT-CS. No differences between untreated and NHT-CS treated lung tissue upon histological examination were observed.
The results indicated the inhaled NHT-CS is a viable preclinical option for developing novel inhalation formulations as a potential anti-smoking therapeutic.
本研究旨在通过 C57BL/6 小鼠的运动活性评估干粉吸入剂制剂中尼古丁的控释活性。
为了实现这一目标，我们构建了一种用于向小鼠肺部给药尼古丁的鼻内吸入装置，并确定了最佳操作参数。我们使用运动活性测试比较了载有尼古丁酒石酸氢盐的壳聚糖纳米粒子（NHT-CS）与 NHT 在 C57BL/6 小鼠中的作用。比较了改变运动活性所需的 NHT-CS 的最小吸入剂量与吸入和皮下（s.c.）注射 NHT 的剂量。最后，对肺组织进行组织学检查，以确保吸入 NHT-CS 不会造成肺部损伤。
我们发现，流速为 0.9 L/min，暴露时间为 5 min 时，尼古丁的输送效果最佳。需要至少吸入 0.88 mg 的 NHT-CS 或 0.59 mg 的 NHT，才能与注射 0.5 mg/kg 尼古丁产生相似的运动活性，这表明制剂过程没有改变 NHT-CS 的活性。组织学检查未观察到未处理和 NHT-CS 处理的肺组织之间的差异。
结果表明，吸入 NHT-CS 是开发新型吸入制剂作为潜在戒烟治疗方法的可行临床前选择。
