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Antiparasitic properties of miltefosine-based nanoformulations against protozoan pathogen, Acanthamoeba castellanii
Noor Akbar1, Roberta Cagliani2, Jibran Sualeh Muhammad3, Mutasem Rawas-Qalaji4, Balsam Qubais Saeed5, Naveed Ahmed Khan6, Ruqaiyyah Siddiqui7
1 Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, Unites Arab Emirates; Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates; Department of Biology, Chemistry and Environmental Sciences, College of Arts and Sciences, American University of Sharjah, Sharjah, United Arab Emirates
2 Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
3 Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, Unites Arab Emirates; Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates; Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
4 Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates; Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates; Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA
5 Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, Unites Arab Emirates
6 Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, Unites Arab Emirates; Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
7 Department of Biology, Chemistry and Environmental Sciences, College of Arts and Sciences, American University of Sharjah, Sharjah, United Arab Emirates
Correspondence Address:
Dr. Jibran Sualeh Muhammad
Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272
United Arab Emirates
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/abhs.abhs_35_22
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Background: Acanthamoeba castellanii genotype T4 is the causative agent of the progressively increasing sight-threatening Acanthamoeba keratitis and central nervous system infections. Because of the increased prevalence and the ineffectiveness of the current antiamoebic drugs, we synthesized miltefosine poly(lactic-co-glycolic acid) nanoparticles (miltefosine PLGA NP) as a potential potent and biocompatible antiamoebic drug. The advantage to use PLGA NP is to preserve the cells from the toxic effect of miltefosine drug. In particular, miltefosine PLGA nanoformulation offers a better cellular uptake and a sustained drug release compared with the free drug that presents potent cytotoxicity at high concentrations against human colon cancer cell lines. Methods: The miltefosine NP were synthesized using a double emulsion-solvent evaporation method, characterized, and then assessed for their antiamoebic activity against A. castellanii belonging to the T4 genotype. Blank PLGA NP and miltefosine were used as controls. Results: Amoebicidal assays revealed that at 25 and 50 µM, unmodified miltefosine eradicated 83% and 93% of amoebae, respectively. At these same concentrations of 25 and 50 µM, the amount of miltefosine released form PLGA NP formulation was limited to 22.6%. However, it killed 36% and 56% of the protozoa, respectively. Thus, the efficacy of PLGA NP formulation was similar to that of the unmodified miltefosine. Both miltefosine and its PLGA NP significantly inhibited the pretreated amoebae (minimum inhibitory concentration 50% = 37.23 and 55.26 µM, respectively, compared with 147.2 µM of the blank NP; P < 0.05) and reduced amoebae-mediated host cell death. The blank NP and miltefosine NP exhibited minimal cytotoxicity against colon epithelial cell lines. In contrast, the unmodified miltefosine caused 37%, 71%, and 88% of cytotoxicity at 10, 25, and 50 µM, respectively. Conclusion: Overall, these findings suggest that controlling the release of miltefosine from PLGA NP for a short time was almost as effective as miltefosine alone against A. castellanii genotype T4 while reducing host cell toxicity. Hence, this study demonstrates the feasibility of using PLGA NP for the treatment of Acanthamoebic infections. |
