Faculty of Pharmacy, Antiparasite Chemotherapy, UMR 8076 CNRS BioCIS, University Paris-Saclay , Chatenay-Malabry , France.
Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais (UFMG) , Belo Horizonte , Brazil.
Expert Opin Drug Deliv. 2019 Oct;16(10):1063-1079. doi: 10.1080/17425247.2019.1659243. Epub 2019 Aug 30.
: Among the drugs in clinical use for the treatment of leishmaniases, amphotericin B (AmB) is the most effective and has been the most extensively studied for the development of drug delivery strategies. Liposomal amphotericin B (AmBisome®) still represents the best therapeutic option for leishmaniases, however, its clinical efficacy depends on the patient immunological status and the endemic region. Moreover, the need for parenteral administration, its side effects and high cost significantly limit its use in developing countries. : This article provides insight into the novel drug delivery strategies that were investigated for AmB over the last 5 years and a final critical selection of emerging concepts and most promising approaches, based on the significance of preclinical antileishmanial and toxicity data. : The feasibility of oral and topical delivery of AmB has been established in experimental models of leishmaniases. Highly effective AmB nanocarriers containing active targeting ligand and/or immunomodulatory component have also emerged. Translating these advances to the clinic still relies on the full demonstration of safety and efficacy in humans and on the viability and cost-effectiveness of large-scale industrial production.
在用于治疗利什曼病的临床药物中，两性霉素 B（AmB）是最有效的，并且针对其开发药物输送策略的研究也最为广泛。脂质体两性霉素 B（AmBisome®）仍然是利什曼病的最佳治疗选择，但是，其临床疗效取决于患者的免疫状态和流行地区。此外，需要进行肠胃外给药、存在副作用以及费用高昂，这极大地限制了其在发展中国家的使用。本文深入探讨了过去 5 年中针对两性霉素 B 进行的新型药物输送策略，并根据临床前抗利什曼原虫和毒性数据的重要性，对新兴概念和最有前途的方法进行了最终的批判性选择。在利什曼病的实验模型中已经证实了两性霉素 B 的口服和局部递送的可行性。具有主动靶向配体和/或免疫调节成分的高效两性霉素 B 纳米载体也已出现。将这些进展转化为临床应用仍然依赖于在人体中充分证明安全性和疗效，以及大规模工业生产的可行性和成本效益。
