Chitosan nanoparticles improve the effectivity of miltefosine against Acanthamoeba

Alireza Latifi; Fariba Esmaeili; Mehdi Mohebali; Setayesh Yasami-Khiabani; Mostafa Rezaeian; Mohammad Soleimani; Elham Kazemirad; Amir Amani

doi:10.1371/journal.pntd.0011976

Chitosan nanoparticles improve the effectivity of miltefosine against Acanthamoeba

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

Authors

Alireza Latifi¹, Fariba Esmaeili², Mehdi Mohebali^{1

3}, Setayesh Yasami-Khiabani⁴, Mostafa Rezaeian¹, Mohammad Soleimani⁵, Elham Kazemirad¹, Amir Amani⁶

Affiliations

¹ Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
² Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
³ Center for Research of Endemic Parasites of Iran (CREPI), Tehran University of Medical Sciences, Tehran, Iran.
⁴ Department of Parasitology, Pasteur Institute of Iran, Tehran, Iran.
⁵ Department of Ocular Trauma and Emergency, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
⁶ Natural products and medicinal plants Research center, North Khorasan University of Medical Sciences, Bojnurd, Iran.

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.

Copyright: © 2024 Latifi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

MeSH terms

Acanthamoeba*
Animals
Chitosan* / pharmacology
Drug Carriers
Nanoparticles*
Phosphorylcholine / analogs & derivatives*
Rabbits

Substances

Drug Carriers
Chitosan
miltefosine
Phosphorylcholine

Grants and funding

This research has been supported by Tehran University of Medical Sciences and Health Services grant no. 99-2-211-49861. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.