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壳聚糖纳米粒提高米替福新抗棘阿米巴的效果。

Chitosan nanoparticles improve the effectivity of miltefosine against Acanthamoeba.

机构信息

Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

PLoS Negl Trop Dis. 2024 Mar 25;18(3):e0011976. doi: 10.1371/journal.pntd.0011976. eCollection 2024 Mar.

DOI:10.1371/journal.pntd.0011976
PMID:38527059
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10962830/
Abstract

BACKGROUND

Acanthamoeba keratitis (AK) is a corneal sight-threatening infection caused by the free-living amoebae of the genus Acanthamoeba. Early and appropriate treatment significantly impacts visual outcomes. Mucoadhesive polymers such as chitosan are a potential strategy to prolong the residence time and bioavailability of the encapsulated drugs in the cornea. Regarding the recent administration of miltefosine (MF) for treating resistant AK, in the present study, we synthesized miltefosine-loaded chitosan nanoparticles (MF-CS-NPs) and evaluated them against Acanthamoeba.

METHODOLOGY/PRINCIPAL FINDINGS: Chitosan nanoparticles (CNPs) were prepared using the ionic gelation method with negatively charged tripolyphosphate (TPP). The zeta-potential (ZP) and the particle size of MF-CS-NPs were 21.8±3.2 mV and 46.61±18.16 nm, respectively. The release profile of MF-CS-NPs indicated linearity with sustained drug release. The cytotoxicity of MF-CS-NPs on the Vero cell line was 2.67 and 1.64 times lower than free MF at 24 and 48 hours. This formulation exhibited no hemolytic activity in vitro and ocular irritation in rabbit eyes. The IC50 of MF-CS-NPs showed a significant reduction by 2.06 and 1.69-fold in trophozoites at 24 and 48 hours compared to free MF. Also, the MF-CS-NPs IC50 in the cysts form was slightly decreased by 1.26 and 1.21-fold at 24 and 48 hours compared to free MF.

CONCLUSIONS

The MF-CS-NPs were more effective against the trophozoites and cysts than free MF. The nano-chitosan formulation was more effective on trophozoites than the cysts form. MF-CS-NPs reduced toxicity and improved the amoebicidal effect of MF. Nano-chitosan could be an ideal carrier that decreases the cytotoxicity of miltefosine. Further analysis in animal settings is needed to evaluate this nano-formulation for clinical ocular drug delivery.

摘要

背景

棘阿米巴角膜炎（AK）是一种由自由生活的棘阿米巴属引起的角膜致盲性感染。早期和适当的治疗对视力结果有显著影响。 壳聚糖等黏膜黏附聚合物是一种延长包封药物在角膜中停留时间和生物利用度的潜在策略。鉴于米替福新（MF）最近用于治疗耐药性 AK，在本研究中，我们合成了负载米替福新的壳聚糖纳米颗粒（MF-CS-NPs）并对其进行了棘阿米巴评估。

方法/主要发现：壳聚糖纳米颗粒（CNPs）采用带负电荷的三聚磷酸钠（TPP）的离子凝胶化法制备。MF-CS-NPs 的 Zeta 电位（ZP）和粒径分别为 21.8±3.2 mV 和 46.61±18.16 nm。MF-CS-NPs 的释放曲线呈线性，药物释放持续。MF-CS-NPs 对 Vero 细胞系的细胞毒性在 24 和 48 小时分别比游离 MF 低 2.67 和 1.64 倍。该制剂在体外无溶血活性，对兔眼无眼刺激性。与游离 MF 相比，MF-CS-NPs 在 24 和 48 小时的滋养体中的 IC50 分别降低了 2.06 和 1.69 倍。此外，MF-CS-NPs 在 24 和 48 小时的包囊形式中的 IC50 分别降低了 1.26 和 1.21 倍。

结论

MF-CS-NPs 对滋养体和包囊的效果优于游离 MF。纳米壳聚糖制剂对滋养体的效果优于包囊形式。MF-CS-NPs 降低了米替福新的毒性并提高了杀阿米巴效果。纳米壳聚糖可能是一种降低米替福新细胞毒性的理想载体。需要在动物模型中进一步分析，以评估这种纳米制剂用于临床眼部药物输送。

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