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基于纳米载体锌铝层状双氢氧化物的盐酸小檗碱递送系统:物理化学表征、释放行为及抗菌潜力评估

Delivery system for berberine chloride based on the nanocarrier ZnAl-layered double hydroxide: Physicochemical characterization, release behavior and evaluation of anti-bacterial potential.

作者信息

Djebbi Mohamed Amine, Elabed Alae, Bouaziz Zaineb, Sadiki Moulay, Elabed Soumya, Namour Philippe, Jaffrezic-Renault Nicole, Amara Abdesslem Ben Haj

机构信息

Laboratoire de Physique des Matériaux Lamellaires et Nano-Matériaux Hybrides, Faculté des Sciences de Bizerte, Université de Carthage, 7021 Bizerte, Tunisia; Institut des Sciences Analytiques UMR CNRS 5280, Université Claude Bernard-Lyon 1, 5 Rue de la Doua, 69100 Villeurbanne, France.

Laboratoire de Biotechnologie Microbienne, Faculté des Sciences et Techniques de Fès, Université Sidi Mohamed Ben Abdellah, 1213 Fès-Saïs, Morocco.

出版信息

Int J Pharm. 2016 Dec 30;515(1-2):422-430. doi: 10.1016/j.ijpharm.2016.09.089. Epub 2016 Oct 19.

Abstract

Layered double hydroxide (LDH) has attracted major interest as one of the most versatile drug delivery systems especially for adsorption capacity and/or controlled delivery property of bioactive agents owing to their combining features of biohybrid. ZnAl synthesized layered double hydroxide can offer a platform to immobilize various types of bioactive compounds, particularly berberine chloride (BBC). However, the immobilization reaction of berberine chloride into ZnAl-LDH was performed by direct co-precipitation method at different ratios of BBC/LDH. BBC-ZnAl-LDH biohybrids were characterized in terms of structure, surface morphology, in vitro drug release profile and antibacterial assay against various bacterial cells. The BBC biomolecules were attached by coordinate bond. Structural and microstructural characterization confirms that interaction of BBC with ZnAl-LDH occurs by adsorption rather than intercalation of BBC within LDH layers. The BBC release profiles from BBC-ZnAl-LDH had a longer release duration compared to the physical mixture, and the drug release seemed faster with the low ratio of BBC/LDH. BBC-ZnAl-LDH can be internalized into bacterial cells. In vitro experiments in PBS medium showed that BBC-ZnAl-LDH biohybrid had higher cytotoxicity and inhibitory effects against three pathogenic bacteria; Staphylococcus aureus CIP 543154, Pseudomonas aeruginosa A22 and Bacillus subtilus ILP 1428B upon the drug release profiles and its destructive potential depends on the loading BBC on the LDH layers. Nonetheless these results prove that the prepared BBC-ZnAl-LDH biohybrids retain the anti-bacterial character of the BBC molecules and are therefore potential modified drug delivery system (DDS).

摘要

层状双氢氧化物(LDH)作为最通用的药物递送系统之一,因其生物杂化的综合特性,特别是生物活性剂的吸附能力和/或控释特性,而备受关注。合成的锌铝层状双氢氧化物可以提供一个平台来固定各种类型的生物活性化合物,特别是盐酸小檗碱(BBC)。然而,通过直接共沉淀法以不同的BBC/LDH比例进行了盐酸小檗碱在ZnAl-LDH中的固定化反应。对BBC-ZnAl-LDH生物杂化物进行了结构、表面形态、体外药物释放曲线以及针对各种细菌细胞的抗菌测定等方面的表征。BBC生物分子通过配位键连接。结构和微观结构表征证实,BBC与ZnAl-LDH的相互作用是通过吸附发生的,而不是BBC插入LDH层内。与物理混合物相比,BBC-ZnAl-LDH的BBC释放曲线具有更长的释放持续时间,并且在BBC/LDH比例较低时药物释放似乎更快。BBC-ZnAl-LDH可以内化到细菌细胞中。在PBS培养基中的体外实验表明,BBC-ZnAl-LDH生物杂化物对三种致病细菌;金黄色葡萄球菌CIP 543154、铜绿假单胞菌A22和枯草芽孢杆菌ILP 1428B具有更高的细胞毒性和抑制作用,其药物释放曲线及其破坏潜力取决于LDH层上负载的BBC。尽管如此,这些结果证明所制备的BBC-ZnAl-LDH生物杂化物保留了BBC分子的抗菌特性,因此是潜在的改性药物递送系统(DDS)。

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