The advantages of nanomedicine in the treatment of visceral leishmaniasis: between sound arguments and wishful thinking

ABSTRACT

Introduction: Although life-threatening if left untreated, visceral leishmaniasis (VL) is still a neglected endemic disease in 98 countries worldwide. The number of drugs available is low and few are in clinical trials. In the last decades, efforts have been made on the development of nanocarriers as drug delivery systems to treat VL. Given the preferential intracellular location of the parasite in the liver and spleen macrophages, the rationale is sturdy. In a clinical setting, liposomal amphotericin B displays astonishing cure rates.

Areas covered: A literature search was performed through PubMed and Google Scholar. We critically reviewed the main literature highlighting the success of nanomedicine in VL. We also reviewed the hurdles and yet unfulfilled promises rising awareness of potential drawbacks of nanomedicine in VL.

Expert opinion: VL is a disease where nanomedicines successes shine through. However, there are a lot of obstacles on the road to developing more efficient strategies such as targeting functionalization, oral formulations, or combined therapies. And those strategies raise many questions.

KEYWORDS:

• Visceral leishmaniasis
• liposomal amphotericin B
• bioavailability
• targeting
• oral form
• Miltefosine
• nanomedicine

Article Highlights

• LAmB is unequivocally a success of nanomedicine and fulfills a lot of promises (Increased efficacy, modified pharmacokinetics & reduced toxicity)

• The spectacular efficiency of LAmB in the Indian Sub-continent is not seen in East Africa for instance, leaving room for other intravenous nanocarriers encapsulating other antileishmanials.

• Given the hurdles (plasma proteins, complexity in the manufacturing, efficacy of passive targeting), is the active targeting strategy towards the macrophage a necessity in nanomedicines destined to treat VL? Nanomedicines could be an efficient method to circumvent drug resistances by increasing the intracellular concentration of the drug and limiting the action of efflux proteins.

• Combined therapies being either nanobased or not are a good idea, fixed associations in a single nanocarrier might not be ideal in VL and might favor resistances appearance It is well accepted in the Health Science community that an oral form is preferable to an injectable form, however there is lessons to draw from miltefosine (Impavido®) real life use. In poverty context, is a 2 to 4 weeks regimen of oral form preferable to a single shot injection? Even though the neglected market is not the priority for pharmaceutical companies, there are still appealing alternatives to develop VL drugs (differential pricing stratification, priority review voucher).

• There is still room for intravenous injectable nanocarrier development against VL.

Acknowledgments

The Figures 1 & 3 were created using Biorender.com

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

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Reviewer disclosures

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

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This paper was not funded.