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采用 Box-Behnken 设计优化磷酸氯喹纳米结构脂质载体及其抗疟效果。

Optimisation of chloroquine phosphate loaded nanostructured lipid carriers using Box-Behnken design and its antimalarial efficacy.

机构信息

a Department of Pharmaceutics , JSS College of Pharmacy, Affiliated to Jagadguru Sri Shivarathreeswara University-Mysuru , Ootacamund , Tamil Nadu , India.

b Department of Biotechnology and Bioinformatics, School of life Sciences , University of Hyderabad , Hyderabad , Telangana , India.

出版信息

J Drug Target. 2018 Aug;26(7):576-591. doi: 10.1080/1061186X.2017.1390671. Epub 2017 Oct 23.

Abstract

Chloroquine was once the most widely used antimalarial for nearly eight decades for its safety, efficiency, stability, low cost and finally for its less toxic nature. But its use and efficacy got slowly decreased with the increase of chloroquine resistant strains of Plasmodium species throughout the world. Lipid based nanodrug delivery systems have been very popular in the recent times as they are very less toxic, have drug targeting capabilities and also reduces the dosing frequency by increasing efficacy of the drug. In the present research work, response surface methodology was employed to optimise chloroquine phosphate (CQ) loaded nanostructured lipid carriers (NLCs) using a modified double emulsion technique. The optimised CQ loaded NLC showed a particle size of 66.50 ± 1.21 nm, PDI of 0.210 ± 0.016, ZP of +38.4 ± 1.44 and EE of 78.2 ± 1.2%, respectively. The in vitro and in vivo antimalarial studies of CQ loaded NLCs showed an enhanced antimalarial efficacy of the nanoformulation with a better suppression of parasitemia and with an increased efficacy of more than 23% in comparison to pure drug. This study demonstrated that by loading a drug into an NLCs system can help in overcoming the problems associated with the present antimalarials available.

摘要

氯喹在近八十年来因其安全性、有效性、稳定性、低成本,最终因其毒性较小而被广泛用于抗疟。但随着世界各地疟原虫对氯喹耐药株的增加,其使用和疗效逐渐下降。近年来,基于脂质的纳米药物递送系统因其毒性较小、具有药物靶向能力,并且通过提高药物疗效来减少用药频率而非常受欢迎。在本研究工作中,使用改良的双重乳液技术,通过响应面法对载有磷酸氯喹的纳米结构脂质载体(NLC)进行了优化。优化后的载有 CQ 的 NLC 的粒径为 66.50 ± 1.21nm,PDI 为 0.210 ± 0.016,ZP 为+38.4 ± 1.44,EE 为 78.2 ± 1.2%。载有 CQ 的 NLC 的体内外抗疟研究表明,与纯药物相比,纳米制剂具有增强的抗疟效果,能够更好地抑制寄生虫血症,疗效提高了 23%以上。这项研究表明,将药物载入 NLC 系统可以帮助克服目前可用的抗疟药物所存在的问题。

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