Envisioning the Innovations in Nanomedicine to Combat Visceral Leishmaniasis: For Future Theranostic Application

Singh, Om Prakash; Gedda, Mallikarjuna Rao; Mudavath, Shyam Lal; Srivastava, O. N.

doi:10.2217/nnm-2018-0448

Cited by 33 publications

(39 citation statements)

References 71 publications

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“…To overcome the failure of anti-leishmanial drug therapies, the design and development of pertinent drugcarrier systems are of immediate importance. Several drug delivery systems have been developed against VL with enhanced efficacy and reduced toxicity concerns [18][19][20][21][22] . In in vivo, the efficacy of the drug is not solely dependent on its physico-chemical properties, but also the carrier system, which could enhance the bioavailability, concede a localized and controlled release of the drug which endow to the explicit requirements of therapy to maximize efficacy, patient safety and compliance 23 .…”

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confidence: 99%

Modified solid lipid nanoparticles encapsulated with Amphotericin B and Paromomycin: an effective oral combination against experimental murine visceral leishmaniasis

Parvez

Yadagiri

Gedda

et al. 2020

Sci Rep

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The development of an effective oral therapeutics is an immediate need for the control and elimination of visceral leishmaniasis (VL). We exemplify the preparation and optimization of 2-hydroxypropyl-β-cyclodextrin (HPCD) modified solid lipid nanoparticles (SLNs) based oral combinational cargo system of Amphotericin B (AmB) and Paromomycin (PM) against murine VL. The emulsion solvent evaporation method was employed to prepare HPCD modified dual drugloaded solid lipid nanoparticles (m-DDSLNs). The optimized formulations have a mean particle size of 141 ± 3.2 nm, a polydispersity index of 0.248 ± 0.11 and entrapment efficiency for AmB and PM was found to be 96% and 90% respectively. The morphology of m-DDSLNs was confirmed by scanning electron microscopy and transmission electron microscopy. The developed formulations revealed a sustained drug release profile upto 57% (AmB) and 21.5% (PM) within 72 h and were stable at both 4 °C and 25 °C during short term stability studies performed for 2 months. Confocal laser scanning microscopy confirmed complete cellular internalization of SLNs within 24 h of incubation. In vitro cytotoxicity study against J774A.1 macrophage cells confirmed the safety and biocompatibility of the developed formulations. Further, m-DDSLNs did not induce any hepatic/renal toxicities in Swiss albino mice. The in vitro simulated study was performed to check the stability in simulated gastric fluids and simulated intestinal fluids and the release was found almost negligible. The in vitro anti-leishmanial activity of m-DDSLNs (1 µg/ml) has shown a maximum percentage of inhibition (96.22%) on intracellular amastigote growth of L. donovani. m-DDSLNs (20 mg/kg × 5 days, p.o.) has significantly (P < 0.01) reduced the liver parasite burden as compared to miltefosine (3 mg/kg × 5 days, p.o.) in L. donovani-infected BALB/c mice. This work suggests that the superiority of as-prepared m-DDSLNs as a promising approach towards the oral delivery of anti-leishmanial drugs. Visceral leishmaniasis (VL), also known as Kala-Azar is the most severe form of leishmaniasis, a neglected tropical disease caused by the protozoan parasite Leishmania donovani, The disease is transmitted to human host by the bite of an infected female haemo-flagellate sand fly 1. According to WHO, 0.5-0.9 million new VL cases are reported every year, > 95% of which occur in ten countries Bangladesh,

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confidence: 99%

Modified solid lipid nanoparticles encapsulated with Amphotericin B and Paromomycin: an effective oral combination against experimental murine visceral leishmaniasis

Parvez

Yadagiri

Gedda

et al. 2020

Sci Rep

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“…2 Present Address: Department of Botany, Serampore College, Hooghly, Serampore, West Bengal, India. 3 Present Address: Dr. Kanailal Bhattacharyya College, Dharmatala, Ramrajatala, Santragachi, Howrah, West Bengal, India. 4 Department of Tropical Medicine, School of Tropical Medicine, Kolkata, West Bengal, India.…”

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confidence: 99%

“…Despite a reduction in the number of visceral leishmaniasis (VL) cases in previously endemic areas, many regions still show the presence of disease burden and also spread into newer areas has been reported. Early diagnosis with complete treatment of cases, together with the development of a vaccine, should be considered as important solutions [1][2][3]. Clinical diagnosis of VL depends on the demonstration of parasites in spleen or bone marrow aspirates, a complicated procedure to perform, but still considered as the gold standard in routine diagnosis [4].…”

Section: Introductionmentioning

confidence: 99%

Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis

et al. 2020

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Background Visceral leishmaniasis (VL), is a parasitic disease that causes serious medical consequences if treatment is delayed. Despite a decline in the number of VL cases in the Indian subcontinent, the commencement of the disease in newer areas continues to be a major concern. Although serological diagnosis mainly by immunochromatographic tests has been found to be effective, a test of cure in different phases of treatment is still desired. Even though a good prophylactic response has been obtained in murine models by a number of vaccine candidates, few have been proposed for human use. Methods In this study, nine antigenic components (31, 34, 36, 45, 51, 63, 72, 91 and 97 kDa) of Leishmania promastigote membrane antigens (LAg), were electroeluted and evaluated through ELISA to diagnose and distinguish active VL from one month cured and six months post-treatment patients. Further, to investigate the immunogenicity of electroeluted proteins, human PBMCs of cured VL patients were stimulated with 31, 34, 51, 63, 72 and 91 kDa proteins. Results We found that 34 and 51 kDa proteins show 100% sensitivity and specificity with healthy controls and other diseases. After six months post-treatment, antibodies to 72 and 91 kDa antigens show a significant decline to almost normal levels. This suggests that 34 and 51 kDa proteins are efficient in diagnosis, whereas 72 and 91 kDa proteins may be used to monitor treatment outcome. In another assay, 51 and 63 kDa proteins demonstrated maximum ability to upregulate IFN-γ and IL-12 with minimum induction of IL-10 and TGF-β. The results indicating that 51 and 63 kDa proteins could be strong candidates for human immunization against VL. In contrast, 34 and 91 kDa proteins demonstrated a reverse profile and may not be a good vaccine candidate. Conclusions The preliminary data obtained in this study proposes the potential of some of the antigens in Leishmania diagnosis and for test of cure. Additionally, some antigens demonstrated good immunoprophylactic cytokine production through T cell-mediated immune response, suggesting future vaccine candidates for VL. However, further studies are necessary to explore these antigens in diagnosis and to access the long-term immune response.

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“…Despite a reduction in the number of visceral leishmaniasis (VL) cases in previously endemic areas, many regions still show the presence of disease burden and also spread in newer areas has been reported. Early diagnosis with complete treatment of cases together with the development of vaccine should be considered as the important solutions [1,2,3]. Clinical diagnosis of VL depends on the demonstration of parasites in spleen or bone marrow aspirate, a complicated procedure to perform, but still considered as the gold standard in routine diagnosis [4].…”

Section: Introductionmentioning

confidence: 99%

Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis

Ejazi

Ghosh

Bhattacharyya

et al. 2020

Preprint

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Background: Visceral leishmaniasis (VL), a parasitic disease causes serious medical consequences if treatment is delayed. Despite a decline in the number of VL cases in the Indian Subcontinent, the commencement of the disease in newer areas continues to be a major concern. Although serological diagnosis mainly by immunochromatographic tests has been found to be effective, test for cure in different phases of treatment is still desired. Even though a good prophylactic response has been obtained in murine models by a number of vaccine candidates, few have been proposed for human use. Methods: In this study, nine antigenic components (31, 34, 36, 45, 51, 63, 72, 91 and 97 kDa) of Leishmania promastigote membrane antigens, LAg, were electroeluted and evaluated through ELISA to diagnose and distinguish active VL from one month cured and six month past infection. Further, to investigate the immunogenicity of electroeluted proteins, human PBMCs of cured VL patients were stimulated with 31, 34, 51, 63, 72, and 91 kDa proteins. Results: We found that 34 and 51 kDa proteins show 100% sensitivity and specificity with healthy controls and other diseases. After six months post treatment, antibodies to 72 and 91 kDa antigens show a significant decline to almost normal levels. This suggests that 34 and 51 kDa are efficient in diagnosis whereas 72 and 91 kDa may be used to monitor treatment outcome. In another study, 51 and 63 kDa proteins demonstrated maximum ability for up-regulate IFN-g and IL-12 with minimum induction of IL-10 and TGF-β. The results indicating that 51 and 63 kDa proteins could be strong candidates for human immunization against VL. In contrast, 34 and 91 kDa demonstrated a reverse profile and may not be a good vaccine candidate. Conclusions: The preliminary data obtained in this study proposes the potential of some of the antigens in Leishmania diagnosis and for test of cure. Additionally, some antigens demonstrated good immunoprophylactic cytokine production through T cell mediated immune response suggesting future vaccine candidates for VL. However, further studies are necessary to explore these antigens in diagnosis and to access long-term immune response.

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Envisioning the Innovations in Nanomedicine to Combat Visceral Leishmaniasis: For Future Theranostic Application

Cited by 33 publications

References 71 publications

Modified solid lipid nanoparticles encapsulated with Amphotericin B and Paromomycin: an effective oral combination against experimental murine visceral leishmaniasis

Modified solid lipid nanoparticles encapsulated with Amphotericin B and Paromomycin: an effective oral combination against experimental murine visceral leishmaniasis

Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis

Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis

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