Marcelino Henrique Rodrigues, Solgadi Audrey, Chéron Monique, do Egito Eryvaldo Socrates Tabosa, Ponchel Gilles
Graduate Program in Health Sciences (PPgCSa), Federal University of Rio Grande do Norte, Natal/RN 59012-570, Brazil; Institut Galien Paris-Saclay, CNRS UMR 8612, Université Paris-Saclay, Orsay 91190, France; College of Pharmacy, Federal University of Bahia, Salvador/BA 40170-115, Brazil (Recent affiliation).
SFR IPSIT (Paris-Saclay Institute of Therapeutic Innovation), University Paris-Saclay, Orsay 91190, France.
Int J Pharm. 2023 Nov 5;646:123444. doi: 10.1016/j.ijpharm.2023.123444. Epub 2023 Sep 26.
Amphotericin B (AmB) is a potent polyenic antifungal agent with leishmanicidal activity. Due to its low solubility and permeability in the gastrointestinal tract, AmB is usually administered intravenously. In this context, various approaches have been used to try to improve these properties. Some of the systems developed have shown proven successful, but there is still a lack of knowledge about the pathways AmB takes after oral administration. Therefore, the aim of this work was not only to obtain aqueous dispersions containing AmB at different aggregation states, but also to entrap this molecule in nanocarriers, and evaluate the influence of these conditions on the jejunal permeability of AmB. To observe the aggregation states of AmB, physicochemical characterization of AmB-albumin complexes and AmB-loaded formulations was performed. Different degrees of AmB aggregation states were obtained. Thus, permeability tests were performed in the Ussing chamber and a decrease in AmB concentration in the donor compartment was observed. Electrophysiological measurements showed different responses depending on the AmB formulation. In conclusion, although control of the AmB aggregation state was observed by physicochemical characterization, this approach does not seem to have a sufficient effect on AmB permeability, but on its toxicity. For a complete understanding of AmB-loaded nanocarriers, other pathways, such as lymphatic absorption, should also be investigated.
两性霉素B（AmB）是一种具有抗利什曼原虫活性的强效多烯类抗真菌剂。由于其在胃肠道中的低溶解度和低渗透性，AmB通常通过静脉给药。在此背景下，人们采用了各种方法来试图改善这些特性。一些已开发的系统已证明是成功的，但对于AmB口服后的途径仍缺乏了解。因此，这项工作的目的不仅是获得含有处于不同聚集状态的AmB的水分散体，而且要将该分子包封在纳米载体中，并评估这些条件对AmB空肠渗透性的影响。为了观察AmB的聚集状态，对AmB-白蛋白复合物和载有AmB的制剂进行了物理化学表征。获得了不同程度的AmB聚集状态。因此，在尤斯灌流小室中进行了渗透性测试，并观察到供体隔室中AmB浓度降低。电生理测量显示，根据AmB制剂的不同会有不同的反应。总之，虽然通过物理化学表征观察到了对AmB聚集状态的控制，但这种方法似乎对AmB的渗透性没有足够的影响，而是对其毒性有影响。为了全面了解载有AmB的纳米载体，还应研究其他途径，如淋巴吸收。
