丹参酮包封 PLGA 纳米粒的制备及其与冰片联合对认知改善的研究
##plugins.themes.bootstrap3.article.sidebar##
##plugins.themes.bootstrap3.article.main##
摘要
认知功能障碍是中枢神经系统疾病引起的最常见的症状，会导致患者生活质量下降。然而，由于其发病机制不明确以及血脑屏障给药带来的挑战，常用的治疗药物几乎没有表现出令人满意的临床效果。本文的旨在开发一种丹参有效组分与冰片共载纳米粒的治疗方法，从而改善认知功能障碍。首先采用一步溶剂蒸发法将丹参酮 IIA (TanIIA) 和隐丹参酮 (CTan) 这两种丹参的有效组分载于PLGA聚合物材料中，得到丹参有效组分共载聚合物纳米粒 (TC@PLGA/NPs)。在对 TC@PLGA/NPs 进行优化表征的基础上，采用冰片联合给药对 Morris 水迷宫大鼠空间记忆的影响进行探究。本研究结果显示 TC@PLGA/NPs 中 TanIIA 和的 CTan 包封率分别为 85.31±1.28%、86.42±2.07%，载药量分别为 1.24±0.09%、1.53±0.15%。平均纳米粒径为194.2±3.5 nm，贮存稳定性好。差式扫描量热分析结果表明，丹参有效组分能够较好地包载于 PLGA 聚合物中，并不是物理混合。水迷宫行为学实验表明，与其他对照组相比，静脉给药 TC@PLGA/NPs 联合冰片(BNL+TC@PLGA/NPs) 可显著提高阿尔茨海默病 (AD) 模型大鼠的空间学习记忆能力。其中，BNL+TC@PLGA/NPs 可显著缩短东莨菪碱诱导痴呆大鼠的逃避潜伏期和游泳距离，同时降低海马组织中丙二醛 (MDA) 和乙酰胆碱酯酶 (AchE) 的表达。本研究表明将冰片增强血脑屏障药物传递的优势与丹参有效组分共载纳米粒相结合，可显著提高大鼠的学习能力和认知功能。这将为中枢神经系统疾病的治疗提供有效策略。
##plugins.themes.bootstrap3.article.details##
参考
Nezerwa M, Chen T, Fried-Stahl J, Joshi N, Terranova J, Wright R, et al. Universal design with mobile app development: bridging the gap for the forgotten populations. In: 2015 Long Island Systems, Applications and Technology Conference; 2015 May 1; Farmingdale, NY, USA. New York: IEEE; 2015. p. 1-6.
Klich-Rączka A, Piotrowicz K, Mossakowska M, Skalska A, Wizner B, Broczek K, et al. The assessment of cognitive impairment suspected of dementia in Polish elderly people: results of the population-based PolSenior Study. Exp Gerontol. 2014;57(9):233-42.
Sabir S, Roohi N. Association of electrophoretically resolved low molecular weight protein fractions with senile dementia in elderly people. Pak J Zool. 2011;43(4):721-26.
Tian BJ, Wei WS. The contribution of vascular factors to the pathogenesis of alzheimer's disease. Chinese J Clinical Neurosciences. 2014;22(4):445-51. (in Chinese)
Wang Y, Liu ZB, Niu WM. Influence of “Xiusanzhen” electroacupuncture on spatial memory ability and APP, Aβ protein expression in hippocamus of mice with Alzheimer's disease. Shaanxi J Traditional Chinese Medicine. 2018;39(2):139-42. (in Chinese)
Li H, Liu JG, Yao MJ, Zhao WM. Effect of Huannaoyicong prescription to AD rat in learning and memory and hippocampus of Aβ-related protein expression with lipid metabolism. Chinese Journal of Basic Medicine in Traditional Chinese Medicine. 2009;15(5):354-7. (in Chinese)
Lei X, Wang JH, Cheng XR, Zhou WX. Multiple-target agents in the therapy of Alzheimer′s disease: research advances. J Int Pharm Res. 2016;43(2):205-15. (in Chinese)
Xiao XH, Niu M, Wang J. Precision medicine oriented drug R&D and quality control of traditional Chinese medicine. Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology. 2017;19(6):900-5. (in Chinese)
Shen CY, Jiang JG, Yang L, Wang DW, Zhu W. Anti‐ageing active ingredients from herbs and nutraceuticals used in traditional Chinese medicine: pharmacological mechanisms and implications for drug discovery. Br J Pharmacol. 2017;174(11):1395-425.
Liu N, Guo L, Yang J. Role of syndrome elements to name Alzheimer's disease syndrome. Global Traditional Chinese Medicine. 2012;5(7):517-20. (in Chinese)
Cheng Y, Feng J, Yao Q, Wu YH, Zhao FX. Discussion on the treatment of chronic arthritis by blood stasis. Guide of China Medicine. 2013;11(20):275-6. (in Chinese)
Qu Q, Zhang H, Zhao XP, Zhang GS. Professor Pei zhengxue's clinical experience on usage of Salvia miltiorrhiza. World Chinese Medicine. 2013;8(11):1326-8. (in Chinese)
Xu SX, Zhong AQ, Ma HN, Li D, Hu Y, Xu YZ, et al. Neuroprotective effect of salvianolic acid B against cerebral ischemic injury in rats via the CD40/NF-κB pathway associated with suppression of platelets activation and neuroinflammation. Brain Res. 2017;1661:37-48.
Jiang P, Li C, Xiang Z, Jiao B. Tanshinone IIA reduces the risk of Alzheimer's disease by inhibiting iNOS MMP-2 and NF-κBp65 transcription and translation in the temporal lobes of rat models of Alzheimer's disease. Mol Med Rep. 2014;10(2):689-94.
Jiang P, Sun XJ, Xiang ZH, Su XP, Li CB. The effect of tanshinone on the expression of iNOS MMP-2 in temporal of Alzheimer's disease model rats and study on mechanism. Progress in Modern Biomedicine. 2014;14(18):3401-4. (in Chinese)
Ye DF, Li MF, Zhang YH, Wang XH, Liu H, Wu WT, et al. Cryptotanshinone regulates androgen synthesis through the ERK/c-Fos/CYP17 pathway in porcine granulosa cells. Evid Based Complement Alternat Med. 2017;2017:5985703.
Canfield SG, Stebbins MJ, Morales BS, Asai SW, Vatine GD, Svendsen CN, et al. An isogenic blood-brain barrier model comprising brain endothelial cells astrocytes and neurons derived from human induced pluripotent stem cells. J Neurochem. 2017;140(6):874-88.
Thao LQ, Byeon HJ, Lee CK, Lee SH, Lee ES, Choi HG, et al. Pharmaceutical potential of tacrolimus-loaded albumin nanoparticles having targetability to rheumatoid arthritis tissues. Int J Pharm. 2016;497(1–2):268-76.
Wan X, Zheng XY, Pang XY, Pang ZQ, Zhao JJ, Zhang ZM, et al. Lapatinib-loaded human serum albumin nanoparticles for the prevention and treatment of triple-negative breast cancer metastasis to the brain. Oncotarget. 2016;7(23):34038-51.
Zhang JM, Wang D, Wu YH, Li W, Hu YC, Zhao G, et al. Lipid-polymer hybrid nanoparticles for oral delivery of tartary buckwheat flavonoids. J Agric Food Chem. 2018;66(19):4923-32.
Cai H, Wen XX, Wen L, Tirelli N, Zhang X, Zhang Y, et al. Enhanced local bioavailability of single or compound drugs delivery to the inner ear through application of PLGA nanoparticles via round window administration. Int J Nanomedicine. 2014;9:5591-601.
Zou L, Wang D, Hu YC, Fu CM, Li W, Dai L, et al. Drug resistance reversal in ovarian cancer cells of paclitaxel and borneol combination therapy mediated by PEG-PAMAM nanoparticles. Oncotarget. 2017;8(36):60453-68.
Alshamsan A. Nanoprecipitation is more efficient than emulsion solvent evaporation method to encapsulate cucurbitacin I in PLGA nanoparticles. Saudi Pharm J. 2014;22(3):219-22.
Lewis DI. Animal experimentation: implementation and application of the 3Rs. Emerg top life sci. 2019;3(6):675-9.
