Recent advances in amphotericin B delivery strategies for the treatment of leishmaniases

ABSTRACT

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

KEYWORDS:

• AmBisome
• amphotericin B
• chemotherapy
• drug delivery
• immunochemotherapy
• leishmaniasis
• nanocarrier

Article highlights

• Updated informations are provided about the target disease, the clinical manifestation, and the causative agent, the drugs used in the clinics and their limitations, supporting the urgent need for new drugs.

• General concepts of drug delivery systems to improve drug pharmacokinetics and rehabilitate some abandoned active agents are presented.

• An update of the clinical use of AmBisome® against leishmaniases and the current limitations is provided.

• Insight into the novel drug delivery strategies that were investigated for amphotericin B 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 amphotericin B has been established in experimental models of leishmaniases.

• Highly effective amphotericin B nanocarriers containing active targeting ligand and/or immunomodulatory component have emerged.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brazil) under Grant numbers [425332/2018-7 and 305659/2017-0]; Fundação de Amparo a Pesquisa do Estado de Minas Gerais (Brazil) under Grant numbers [APQ-03129-16 and MPR-01057-16]; and Agence Nationale de la Recherche (France) under Grant number [ANR-11-IDEX-0003-02]. F Frezard was recipient of fellowships from Conselho Nacional de Desenvolvimento Científico e Tecnológico and ‘Chaire Jean d’Alembert’ (IdEx Université Paris-Saclay).