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Preparation and Characterization of SDF-1α-Chitosan-Dextran Sulfate Nanoparticles
Published on: January 22, 2015
Chitosan nanoparticles improve the effectivity of miltefosine against Acanthamoeba
Alireza Latifi1, Fariba Esmaeili2, Mehdi Mohebali1,3
1Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
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.
Insights
Miltefosine-loaded chitosan nanoparticles (MF-CS-NPs) show enhanced efficacy against Acanthamoeba keratitis (AK) parasites. This nano-formulation reduces miltefosine toxicity, offering a promising strategy for treating this sight-threatening corneal infection.
Area of Science:
- Ophthalmology
- Nanotechnology
- Infectious Diseases
Background:
- Acanthamoeba keratitis (AK) is a severe corneal infection with significant visual impairment risk.
- Early treatment is crucial for visual outcomes in AK.
- Chitosan nanoparticles offer potential for enhanced drug delivery in ocular infections.
Purpose of the Study:
- To synthesize and evaluate miltefosine-loaded chitosan nanoparticles (MF-CS-NPs) for Acanthamoeba treatment.
- To assess the efficacy and safety of MF-CS-NPs against Acanthamoeba in vitro.
- To investigate the potential of nano-chitosan as a carrier for ocular drug delivery.
Main Methods:
- Miltefosine-loaded chitosan nanoparticles (MF-CS-NPs) were prepared using ionic gelation.
- Particle size, zeta-potential, and drug release profiles were characterized.
- Cytotoxicity, hemolytic activity, ocular irritation, and amoebicidal activity (IC50) were evaluated in vitro and in vivo.
Main Results:
- MF-CS-NPs exhibited sustained drug release with optimal particle size (46.61 nm) and zeta-potential (21.8 mV).
- MF-CS-NPs demonstrated significantly lower cytotoxicity and ocular irritation compared to free miltefosine.
- The nano-formulation showed enhanced amoebicidal activity against both Acanthamoeba trophozoites and cysts.
Conclusions:
- MF-CS-NPs are more effective and less toxic than free miltefosine for treating Acanthamoeba keratitis.
- Nano-chitosan serves as an effective carrier, reducing miltefosine's cytotoxicity.
- Further animal studies are warranted to explore clinical applications of MF-CS-NPs in ocular drug delivery.
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