Maciel-Magalhães Magno, Medeiros Renata Jurema, Guedes Nayara Cecília do Couto, Brito Thais Morais de, Souza Gabriele Fátima de, Canabarro Beatriz Rodrigues, Ferraris Fausto Klabund, Amendoeira Fábio Coelho, Rocha Helvécio Vinicius Antunes, Patricio Beatriz Ferreira de Carvalho, Delgado Isabella Fernandes
Programa de Pós-Graduação em Pesquisa Translacional em Fármacos e Medicamentos (PPG-PTFM), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, Brazil.
Programa de Pós-Graduação em Vigilância Sanitária (PPG-VISA), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, Brazil.
Pharmaceutics. 2025 Jan 16;17(1):116. doi: 10.3390/pharmaceutics17010116.
Amphotericin B (AmB) is a commonly utilized antifungal agent, which is also recommended for the treatment of certain neglected tropical diseases, including leishmaniasis. However, its clinical application is constrained because of its poor oral bioavailability and adverse effects, prompting the investigation of alternative drug delivery systems. Polymeric nanoparticles (PNPs) have gained attention as a potential drug delivery vehicle, providing advantages such as sustained release and enhanced bioavailability, and could have potential as AmB carriers. However, concerns persist regarding nanomaterials' toxicity, requiring more studies. Zebrafish () embryos were used as a valuable model for toxicity testing, especially because of their genetic similarity to humans and standardized developmental assessments. In this study, we produced and characterized AmB loaded and non-loaded PNPs by nanoprecipitation, dynamic light scattering, transmission electron microscopy, atomic force microscopy and spectroscopy. Afterwards, we verified their toxicity through in vitro MTT assays in three cell lines (HEK293, HepG2, and J774 A1) and in vivo tests with zebrafish embryos. In both trials, it was noted that nanoencapsulation of the drug led to increased toxicity when compared to non-encapsulated AmB, possibly indicating that they penetrated the embryo's chorion. Nevertheless, it was demonstrated that the polymers used are safe and they are not the cause of toxicity, neither are the nanostructures per se. Therefore, it is believed that the objective of improving the bioavailability of AmB may have been achieved, and the observed toxicity was probably linked to AmB's ability to destabilize cell membranes.
两性霉素B（AmB）是一种常用的抗真菌药物，也被推荐用于治疗某些被忽视的热带疾病，包括利什曼病。然而，由于其口服生物利用度差和副作用，其临床应用受到限制，这促使人们对替代药物递送系统进行研究。聚合物纳米颗粒（PNPs）作为一种潜在的药物递送载体受到关注，它具有缓释和提高生物利用度等优点，并且可能有潜力作为AmB的载体。然而，关于纳米材料的毒性问题仍然存在，需要更多的研究。斑马鱼胚胎被用作毒性测试的宝贵模型，特别是因为它们与人类具有遗传相似性且发育评估具有标准化。在本研究中，我们通过纳米沉淀法、动态光散射、透射电子显微镜、原子力显微镜和光谱学制备并表征了负载和未负载AmB的PNPs。之后，我们通过在三种细胞系（HEK293、HepG2和J774 A1）中进行体外MTT试验以及对斑马鱼胚胎进行体内试验来验证它们的毒性。在这两项试验中都注意到，与未包封的AmB相比，药物的纳米包封导致毒性增加，这可能表明它们穿透了胚胎的绒毛膜。然而，已证明所使用的聚合物是安全的，它们不是毒性的原因，纳米结构本身也不是。因此，人们认为提高AmB生物利用度的目标可能已经实现，观察到的毒性可能与AmB破坏细胞膜的能力有关。
