Department of Pharmaceutics, Jamia Hamdard, Faculty of Pharmacy , Hamdard Nagar, New Delhi-110062 , India +91 9811312247 ; +011 26059633 ; javedaali@ yahoo.com.
Expert Opin Drug Deliv. 2014 Jun;11(6):827-42. doi: 10.1517/17425247.2014.894504. Epub 2014 Mar 22.
The present work evaluated whether the prepared nanoparticles (NPs) would be able to target the drug to the brain by a non-invasive nasal route enhancing its bioavailability.
Bromocriptine (BRC) chitosan NPs (CS NPs) were prepared by ionic gelation method. The biodistribution, pharmacokinetic parameters and dopamine concentration was analysed by ultra-HPLC/mass spectrometry method. The histopathological examination in haloperidol-induced Parkinson's disease in mice model following intranasal (i.n.) administration was evaluated.
BRC was found stable in all exposed conditions and the percentage accuracy observed for intra-day and inter-day batch samples ranged from 90.5 to 107% and 95.3 to 98.9% for plasma and brain homogenates, respectively. BRC-loaded CS NPs showed greater retention into the nostrils (42 ± 8.5% radioactivity) for about 4 h, whereas the 44 ± 7.5% could be retained up to 1 h for BRC solution. The brain:blood ratios of 0.96 ± 0.05 > 0.73 ± 0.15 > 0.25 ± 0.05 of BRC-loaded CS NPs (i.n.) > BRC solution (i.n.) > BRC-loaded CS NPs (intravenous), respectively, at 0.5 h indicated direct nose-to-brain transport bypassing blood-brain barrier. BRC-loaded CS NPs administered intranasally showed significantly high dopamine concentration (20.65 ± 1.08 ng/ml) as compared to haloperidol-treated mice (10.94 ± 2.16 ng/ml) (p < 0.05). Histopathology of brain sections showed selective degeneration of the dopaminergic neurons in haloperidol-treated mice which was markedly reverted by BRC-loaded CS NPs.
Nanoparticulate drug delivery system could be potentially used as a nose-to-brain drug delivery carrier for the treatment of Parkinson's disease.
本研究旨在评估通过非侵入性鼻腔途径制备的纳米粒子（NPs）是否能够将药物靶向大脑，从而提高其生物利用度。
采用离子凝胶法制备溴隐亭（BRC）壳聚糖 NPs（CS NPs）。采用超高效液相色谱/质谱法分析药物的分布、药代动力学参数和多巴胺浓度。通过在小鼠模型中转录因子 Nurr1 敲除诱导帕金森病，评估鼻腔给予后药物的组织病理学变化。
BRC 在所有暴露条件下均稳定，日内和日间批样品的百分准确度分别在 90.5%至 107%和 95.3%至 98.9%之间，用于血浆和脑匀浆。载 BRC 的 CS NPs 在鼻腔中的滞留时间更长（42 ± 8.5%放射性），约 4 小时，而 BRC 溶液的滞留时间为 44 ± 7.5%，约 1 小时。载 BRC 的 CS NPs（鼻腔）的脑：血比值为 0.96 ± 0.05 > 0.73 ± 0.15 > 0.25 ± 0.05，分别为 BRC-loaded CS NPs（静脉）> BRC 溶液（鼻腔）> BRC-loaded CS NPs（鼻腔），在 0.5 小时时表明药物通过鼻腔直接进入大脑，绕过血脑屏障。与给予氟哌啶醇的小鼠（10.94 ± 2.16 ng/ml）相比，鼻腔给予载 BRC 的 CS NPs 可显著提高多巴胺浓度（20.65 ± 1.08 ng/ml）（p < 0.05）。脑切片的组织病理学检查显示，氟哌啶醇处理的小鼠中多巴胺能神经元选择性退化，而载 BRC 的 CS NPs 可显著逆转这种退化。
纳米药物传递系统可作为治疗帕金森病的鼻腔递药载体。
