乳铁蛋白修饰的载两性霉素B纳米储库对内脏利什曼病的靶向化疗：体外和体内研究

Targeted chemotherapy of visceral leishmaniasis by lactoferrin-appended amphotericin B-loaded nanoreservoir: in vitro and in vivo studies.

作者信息

Asthana Shalini, Gupta Pramod K, Jaiswal Anil K, Dube Anuradha, Chourasia Manish K

机构信息

Pharmaceutics Division, CSIR-Central Drug Research Institute, B 10/1, Sector 10, Jankipuram Extension, Lucknow-226031, India.

出版信息

Nanomedicine (Lond). 2015;10(7):1093-109. doi: 10.2217/nnm.14.182.

DOI:10.2217/nnm.14.182

PMID:25929567

Abstract

AIM

Exploitation of lactoferrin-appended amphotericin B bearing nanoreservoir (LcfPGNP-AmB) for targeted eradication of Leishmania donovani.

MATERIALS & METHODS: LcfPGNP-AmB was architechtured through ionic adsorption of lactoferrin over core poly (d,l-lactide-co-glycolide) nanoparticles and characterized. Anti-Leishmania activity in visceral leishmaniasis models, immunomodulatory potential, biodistribution and toxicity profile were also assessed.

RESULTS

LcfPGNP-AmB (size, 196.0 ± 5.28 nm; zeta-potential, +21.7 ± 1.52 mV; encapsulation efficiency, ∼89%) showed reduced toxicity, increased protective proinflammatory mediators expression and down-regulation of disease-promoting cytokines. Biodistribution study illustrated preferential accumulation of LcfPGNP-AmB in liver and spleen. LcfPGNP-AmB showed augmented antileishmanial activity by significantly reducing (∼88%) splenic parasite burden of infected hamsters, compared with commercial-formulations.

CONCLUSION

Superior efficacy, desired stability and reliable safety of cost-effective LcfPGNP-AmB, suggest its potential for leishmaniasis therapeutics.

摘要

目的

利用负载乳铁蛋白的两性霉素B纳米储库（LcfPGNP-AmB）靶向根除杜氏利什曼原虫。

材料与方法

通过乳铁蛋白在聚（d，l-丙交酯-共-乙交酯）纳米颗粒核心上的离子吸附构建LcfPGNP-AmB并进行表征。还评估了其在内脏利什曼病模型中的抗利什曼原虫活性、免疫调节潜力、生物分布和毒性特征。

结果

LcfPGNP-AmB（尺寸，196.0±5.28nm；ζ电位，+21.7±1.52mV；包封率，约89%）显示出较低的毒性、增加了保护性促炎介质的表达并下调了促疾病细胞因子。生物分布研究表明LcfPGNP-AmB在肝脏和脾脏中优先积累。与市售制剂相比，LcfPGNP-AmB通过显著降低（约88%）感染仓鼠的脾脏寄生虫负荷，显示出增强的抗利什曼原虫活性。