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Review
. 2022 Dec 14:10:1016925.
doi: 10.3389/fbioe.2022.1016925. eCollection 2022.

Limitations of current chemotherapy and future of nanoformulation-based AmB delivery for visceral leishmaniasis-An updated review

Prakash Kumar  1 , Pawan Kumar  1 , Nidhi Singh  2 , Salil Khajuria  1 , Rahul Patel  1 , Vinod Kumar Rajana  1 , Debabrata Mandal  1 , Ravichandiran Velayutham  1   3
Affiliations
Review

Limitations of current chemotherapy and future of nanoformulation-based AmB delivery for visceral leishmaniasis-An updated review

Prakash Kumar et al. Front Bioeng Biotechnol. .

Abstract

Visceral leishmaniasis (VL) is the most lethal of all leishmaniasis diseasesand the second most common parasiticdisease after malaria and,still, categorized as a neglected tropical disease (NTD). According to the latest WHO study, >20 Leishmania species spread 0.7-1.0 million new cases of leishmaniasis each year. VL is caused by the genus, Leishmania donovani (LD), which affects between 50,000 and 90,000 people worldwide each year. Lack of new drug development, increasing drug resistance, toxicity and high cost even with the first line of treatmentof Amphotericin B (AmB), demands new formulation for treatment of VLFurther the lack of a vaccine, allowedthe researchers to develop nanofomulation-based AmB for improved delivery. The limitation of AmB is its kidney and liver toxicity which forced the development of costly liposomal AmB (AmBisome) nanoformulation. Success of AmBisome have inspired and attracted a wide range of AmB nanoformulations ranging from polymeric, solid lipid, liposomal/micellar, metallic, macrophage receptor-targetednanoparticles (NP) and even with sophisticated carbon/quantum dot-based AmBnano delivery systems. Notably, NP-based AmB delivery has shown increased efficacy due to increased uptake, on-target delivery and synergistic impact of NP and AmB. In this review, we have discussed the different forms of leishmaniasis disease and their current treatment options with limitations. The discovery, mechanism of action of AmB, clinical status of AmB and improvement with AmBisome over fungizone (AmB-deoxycholate)for VL treatment was further discussed. At last, the development of various AmB nanoformulation was discussed along with its adavantages over traditional chemotherapy-based delivery.

Keywords: amphotericin B; clinical status; drug delivery; leishmaniasis; nanoparticle.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

None
The nanoparticles with different size, shape and structure for drug delivery against Leishmania donovani.
FIGURE 1
FIGURE 1
The mechanism of action of AmB against promastigotes and intracellular amastigotes. Depletion of ergosterol, membrane damage with LDH release, disruption of redox homeostasis with reduced thiol content in promastogtes and increased RNS production along with increased Th1/decreased Th2 response in amastigotes reflects AmB-mediated death.
FIGURE 2
FIGURE 2
Pictorial presentation of AmB-mediated nephrotoxicity caused by ergosterol binding and depletion from glomerular membrane of nephron by dimeric insoluble form of AmB.
FIGURE 3
FIGURE 3
Schematic presentation of major nano formulation based delivery of AmB.
See this image and copyright information in PMC

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