ArticleJournal of experimental pharmacology2025
Biocompatibility and Effectiveness of Amphotericin B-Loaded Metal-Organic Structures (AmB-ZIF-8) as Dermal Drug Transporters in Experimental Cutaneous Leishmaniasis.
Article in Journal of experimental pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
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4 authors.
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Abstract
Purpose: Information on metal-organic frameworks (MOFs) as topical drug delivery systems (DDS) for antileishmanial drugs is limited. This study outlines our strategies for developing MOF-drug conjugate as a topical treatment for cutaneous leishmaniasis (CL) in mice infected with Methods: We selected conjugates from two commercial MOFs (ZIF-8 and Fe-BTC) and seven antileishmanial compounds. Amphotericin B (AmB) and zeolitic imidazolate framework-8 (AmB@ZIF-8) were chosen and prepared at an AmB: ZIF-8 ratio of 1.5:1.0 using the impregnation method. Conjugates were characterised using dynamic light scattering, UV-Vis, FTIR, and SEM. Hydrogels were prepared and evaluated for toxicity and efficacy in CL-BALB/c mice. Results: AmB@ZIF-8 exhibited a 59.6% loading capacity, 6.67% encapsulation efficiency, and 2% in vitro drug release (IVR). The particle size of AmB@ZIF-8 was smaller and more polydisperse than ZIF-8 (1370 nm vs 2537 nm). The conjugation of AmB to ZIF-8 was demonstrated. AmB@ZIF-8 exhibited similar antileishmanial activity to AmB against promastigotes. Topical 0.5% AmB@ZIF-8 and 0.5% AmB hydrogels, administered for 30 days, were unable to decrease lesion sizes or parasite loads. Initially, there was stabilisation of the lesion size; however, the lesions subsequently increased considerably during the 30-day follow-up period. The MOF-hydrogel treatment was non-irritating. Conclusion: There were very low EE% and AmB IVR. AmB@ZIF-8 and AmB hydrogels were found to be safe but ineffective against CL-infected mice. Several factors may explain these negative results, including the large size of the commercial ZIF-8, the aggregation of AmB in solution, the excess AmB used for impregnation, and the conditions of the IVR assay. We suggest continuing to use ZIF-8 as a DDS due to its sensitivity to acidic pH levels; however, we recommend reducing the particle size and lowering the drug-to-ZIF-8 ratio. Other alternatives are discussed in the present paper. We also advocate investigating alternative antileishmanial drugs as cargo, such as miltefosine or pentamidine.
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