Evaluation of rat striatal L-dopa and DA concentration after intraperitoneal administration of L-dopa prodrugs in liposomal formulations
Evaluation of rat striatal L-dopa and DA concentration after intraperitoneal administration of L-dopa prodrugs in liposomal formulations
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DOI：
10.1016/j.jconrel.2004.07.010
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发表时间：
2004-09-30
影响因子：
10.8
通讯作者：
Santucci, E
中科院分区：
文献类型：
--
作者：
Di Stefano, A;Carafa, M;Santucci, E
帕金森病是一种神经退行性疾病，其症状可通过服用左旋多巴 (LD) 来缓解，左旋多巴 (LD) 可以被神经元芳香族 L-氨基酸脱羧酶 (AADC) 转化，从而恢复存活神经元中的多巴胺 (DA) 水平。为了尽量减少不利的副作用，我们研究了新的二聚 LD 衍生物，作为帕金森氏症治疗的潜在前药。为了提高合成前药的生物利用度，将它们封装在二甲酰磷脂酰胆碱（DMPC）和胆固醇（CHOL）的单层脂质体中。体内微透析用于监测腹腔注射后纹状体 LD 和 DA 浓度。新的交付系统的管理。生物利用度评价采用HPLC-EC法进行。腹腔注射后纹状体 LD 和 DA 水平显着升高。给予前药(+)-1b([(O,O-二乙酰)-L-多巴-甲酯]-琥珀酰二酰胺)的脂质体制剂。该制剂显示透析液大鼠纹状体中 DA 基础水平增加了约 2.5 倍，表明 (+)-1b 的脂质体制剂相对于 LD 本身或游离前药 (+)-1b 的等摩尔给药显着增加了 LD 和 DA 浓度。 (C) 2004 Elsevier B.V. 保留所有权利。
Parkinson's disease is a neurodegenerative disease and its symptoms are relieved by administration of L-dopa (LD), which is converted by neuronal aromatic L-aminoacid decarboxylase (AADC), restoring dopamine (DA) levels in surviving neurons. In order to minimize unfavourable side effects, we studied new dimeric LD derivatives, as potential prodrugs for Parkinson's therapeutic treatment. To improve the bioavailability of the synthesized prodrugs, they were encapsulated in unilamellar liposomes of dimiristoylphosphatidylcholine (DMPC) and cholesterol (CHOL). In vivo microdialysis was used to monitor the striatal LD and DA concentrations after i.p. administration of new delivery systems. Bioavailability evaluation was performed by means of the HPLC-EC method. The striatal levels of LD and DA were remarkably elevated after i.p. administration of liposomal formulation of prodrug (+)-1b ([(O,O-diacetyl)-L-dopa-methylester]-succinyldiamide). This formulation showed about 2.5-fold increase in the basal levels of DA in dialysate rat striatum, suggesting that liposomal formulation of (+)-1b significantly increases LD and DA concentrations with respect to equimolar administration of LD itself or free prodrug (+)-1b. (C) 2004 Elsevier B.V. All rights reserved.