In Vitro and in Vivo Optimization of Phase Sensitive Smart Polymer for Controlled Delivery of Rivastigmine for Treatment of Alzheimer's Disease.
In Vitro and in Vivo Optimization of Phase Sensitive Smart Polymer for Controlled Delivery of Rivastigmine for Treatment of Alzheimer's Disease.
复制标题
用于控制卡巴拉汀递送以治疗阿尔茨海默病的相敏智能聚合物的体外和体内优化。
DOI：
10.1007/s11095-020-2757-6
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发表时间：
2020
影响因子：
3.7
通讯作者：
Singh,Jagdish
中科院分区：
文献类型：
--
作者：
Lipp,Lindsey;Sharma,Divya;Banerjee,Amrita;Singh,Jagdish
阿尔茨海默病是一种神经退行性疾病，是最常见的痴呆症，全世界有3500多万人患有此病。利瓦斯汀是一种广泛用于改善阿尔茨海默病临床表现的药物。然而，目前的治疗需要频繁给药，要么口服，要么经皮贴片，这会导致依从性问题和给药错误，有可能产生严重的不良反应。我们的目标是开发一种基于智能聚合物的递送系统，用于在单次皮下注射后的较长时间内控释利瓦斯汀。方法通过聚合物浓度、聚合物组成、药物浓度、溶剂组成、药物疏水性（酒石酸利瓦斯汀碱）等关键因素对利瓦斯汀的释放进行优化。对优化后的体外配方进行了体内安全性和有效性评价。结果采用聚乳酸（50:50）：5%w/vin: 95:5苯甲酸制备的制剂具有良好的体外控释特性。该制剂具有7天的体内缓释效果，具有良好的生物相容性和14天的乙酰胆碱酯酶抑制效果。结论采用相敏智能聚合物制备了易注射的利瓦斯汀控释制剂。优化后的配方显着增加了给药间隔，并可能提高患者的依从性以及阿尔茨海默病患者的生活质量。
PurposeAlzheimer’s disease is a neurodegenerative disorder, and most common form of dementia afflicting over 35 million people worldwide. Rivastigmine is a widely used therapeutic for ameliorating clinical manifestations of Alzheimer’s disease. However, current treatments require frequent dosing either orally orviatransdermal patch that lead to compliance issues and administration errors risking serious adverse effects. Our objective was to develop a smart polymer based delivery system for controlled release of rivastigmine over an extended period following a single subcutaneous injection.MethodsRivastigmine release was optimized by tailoring critical factors including polymer concentration, polymer composition, drug concentration, solvent composition, and drug hydrophobicity (rivastigmine tartratevsbase). Optimizedin vitroformulation was evaluatedin vivofor safety and efficacy.ResultsFormulation prepared using PLGA (50:50) at 5%w/vin 95:5 benzyl benzoate: benzoic acid demonstrated desirable controlled drug release characteristicsin vitro. The formulation demonstrated sustained release of rivastigmine tartrate for 7 daysin vivowith promising biocompatibility and acetylcholinesterase inhibition efficacy for 14 days.ConclusionThe results exemplify an easily injectable controlled release formulation of rivastigmine prepared using phase-sensitive smart polymer. The optimized formulation significantly increases the dosing interval, and can potentially improve patient compliance as well as quality of life of patients living with Alzheimer’s disease.