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用于左旋多巴控释的分子印迹环糊精纳米海绵:帕金森病治疗的前景

Molecularly imprinted cyclodextrin nanosponges for the controlled delivery of L-DOPA: perspectives for the treatment of Parkinson's disease.

作者信息

Trotta Francesco, Caldera Fabrizio, Cavalli Roberta, Soster Marco, Riedo Chiara, Biasizzo Miriam, Uccello Barretta Gloria, Balzano Federica, Brunella Valentina

机构信息

a Dipartimento di Chimica , University of Torino , Torino , Italy.

b Dipartimento di Scienza e Tecnologia del Farmaco , University of Torino , Torino , Italy.

出版信息

Expert Opin Drug Deliv. 2016 Dec;13(12):1671-1680. doi: 10.1080/17425247.2017.1248398. Epub 2016 Oct 24.

Abstract

BACKGROUND

L-DOPA is an amino acid precursor to the neurotransmitter dopamine that is extensively used as a prodrug for the treatment of Parkinson's disease. However, L-DOPA is an unstable compound: when exposed to light or added to aqueous solutions, it may degrade, compromising its therapeutic properties.

METHODS

In this work, a new type of drug-loaded cyclodextrin-based nanosponge, obtained using molecular imprinting, is described for the prolonged and controlled release of L-DOPA. The molecularly imprinted nanosponges (MIP-NSs) were synthesized by cross-linking β-cyclodextrin with 1,1'-carbonyldiimidazole in DMF in the presence of L-DOPA as a template molecule. TGA, DSC and FTIR analyses were performed to characterize the interactions between L-DOPA and the two nanosponge structures. Quantitative NMR spectroscopy was used to determine the amount and the affinity of L-DOPA entrapped in the nanosponges. The in vitro L-DOPA release kinetics from the NSs were quantitatively determined by HPLC analysis.

RESULTS

The MIP-NSs show a slower and more prolonged release profile than the non-imprinted nanosponges. No degradation of the L-DOPA hosted in the MIP-NSs was observed after long-term storage at room temperature.

CONCLUSIONS

The MIP-NSs are a promising alternative for the storage and controlled delivery of L-DOPA.

摘要

背景

左旋多巴是神经递质多巴胺的氨基酸前体,被广泛用作治疗帕金森病的前体药物。然而,左旋多巴是一种不稳定的化合物:当暴露于光下或添加到水溶液中时,它可能会降解,从而损害其治疗特性。

方法

在这项工作中,描述了一种使用分子印迹技术制备的新型载药环糊精基纳米海绵,用于左旋多巴的长效控释。分子印迹纳米海绵(MIP-NSs)通过在作为模板分子的左旋多巴存在下,在二甲基甲酰胺中将β-环糊精与1,1'-羰基二咪唑交联合成。进行热重分析(TGA)、差示扫描量热法(DSC)和傅里叶变换红外光谱(FTIR)分析,以表征左旋多巴与两种纳米海绵结构之间的相互作用。使用定量核磁共振光谱法测定包封在纳米海绵中的左旋多巴的量和亲和力。通过高效液相色谱(HPLC)分析定量测定纳米海绵中左旋多巴的体外释放动力学。

结果

与非印迹纳米海绵相比,MIP-NSs显示出更缓慢、更持久的释放曲线。在室温下长期储存后,未观察到MIP-NSs中所含左旋多巴的降解。

结论

MIP-NSs是左旋多巴储存和控释的一种有前景的替代方案。

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