Singh Shailendra Kumar, Mishra Dina Nath
Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, 125001, Haryana, India.
Curr Drug Deliv. 2019;16(1):51-58. doi: 10.2174/1567201815666181004094707.
Presence of blood brain barrier is one of the major hurdle in drug delivery to brain for the treatment of neurological diseases. Alternative and more effective drug delivery approaches have been investigated for the drug targeting to brain in therapeutic range.
The present investigation was carried out to improve the galantamine bioavailability in brain by intranasal drug delivery through thiolated chitosan nanoparticles and compared to nasal and oral delivery of its solution using pharmacodynamic activity as well as biochemical estimation.
Thiolated chitosan (modified) nanoparticles were fabricated using modified ionic gelation method and intranasal delivery is evaluated by reversal of scopolamine induced amnesia and biochemical estimation of acetylcholinesterase activity in Swiss albino mice brain. Scopolamine (0.4 mg/kg, i.p.) was used to induce amnesia. Piracetam (400mg/kg, i.p.) was used as positive control. Mice were treated with galantamine solution (4mg/kg) by oral and nasal route and formulated galantamine nanoparticles (equivalent to 4mg/kg) by intranasal administration for 7 successive days and the results were compared statistically.
Intranasal delivery of galantamine loaded thiolated chitosan nanoparticles was found significant (p<0.05) as compared to oral and nasal administration of its solution, by pharmacodynamic study and biochemical estimation of acetylcholinesterase activity in Swiss albino mice brain.
Significant recovery in amnesia induced mice model by intranasal administration of galantamine loaded thiolated chitosan nanoparticles established the relevance of nose to brain delivery over the conventional oral therapies for the treatment of Alzheimer's disease.
血脑屏障的存在是治疗神经疾病的药物向脑内递送的主要障碍之一。人们已经研究了其他更有效的药物递送方法，以便在治疗范围内将药物靶向递送至脑。
本研究旨在通过经硫醇化壳聚糖纳米粒鼻内给药来提高加兰他敏在脑内的生物利用度，并通过药效学活性以及生化评估，将其与加兰他敏溶液的鼻内和口服给药进行比较。
采用改良离子凝胶法制备硫醇化（修饰）壳聚糖纳米粒，并通过东莨菪碱诱导的记忆缺失的逆转以及瑞士白化小鼠脑内乙酰胆碱酯酶活性的生化评估来评价鼻内给药效果。使用东莨菪碱（0.4mg/kg，腹腔注射）诱导记忆缺失。吡拉西坦（400mg/kg，腹腔注射）用作阳性对照。小鼠连续7天经口服和鼻内途径给予加兰他敏溶液（4mg/kg），并经鼻内给予配制的加兰他敏纳米粒（相当于4mg/kg），对结果进行统计学比较。
通过药效学研究以及瑞士白化小鼠脑内乙酰胆碱酯酶活性的生化评估发现，与加兰他敏溶液的口服和鼻内给药相比，经鼻内给予载有加兰他敏的硫醇化壳聚糖纳米粒具有显著差异（p<0.05）。
经鼻内给予载有加兰他敏的硫醇化壳聚糖纳米粒可使记忆缺失诱导小鼠模型显著恢复，这证实了与传统口服疗法相比，鼻脑给药在治疗阿尔茨海默病方面的相关性。
