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Effect of Amphotericin B Nanodisks on Leishmania major Infected Mice.

Cole P, Bishop J, Beckstead J, Titus R, Ryan R - Pharm Anal Acta (2014)

Bottom Line: Balb/c and CH3 mice infected with Leishmania major on Day 0 were administered vehicle alone, empty ND or AMB-ND on Day 1 and day 7, via the tail vein.Mice were sacrificed 25 or 50 days post inoculation and tissue histology evaluated.It may be inferred that AMB-ND may be useful for prophylactic and/or treatment of early stage Leishmania spp. infection.

View Article: PubMed Central - HTML - PubMed

Affiliation: Microbiology, Immunology, and Pathology Department, Colorado State University, Fort Collins, CO 80523-1619.

ABSTRACT

Objective: To assess the efficacy of a novel formulation of the polyene antibiotic, amphotericin B (AMB), as therapy for cutaneous leishmaniasis in different mouse strains.

Methods: (AMB), was formulated into water-soluble transport particles, termed nanodisks (ND). Balb/c and CH3 mice infected with Leishmania major on Day 0 were administered vehicle alone, empty ND or AMB-ND on Day 1 and day 7, via the tail vein. Mice were sacrificed 25 or 50 days post inoculation and tissue histology evaluated. Balb/c mice treated with vehicle or empty ND showed signs of severe infection while CH3 mice had less inflammation and fewer parasites. AMB-ND treatment (2 mg/kg) had a marked therapeutic effect on L. major infected Balb/c mice and a discernable therapeutic benefit on CH3 mice.

Conclusions: AMB-ND is efficacious in the treatment of cutaneous leishmaniasis in both susceptible and resistant mouse strains. It may be inferred that AMB-ND may be useful for prophylactic and/or treatment of early stage Leishmania spp. infection.

No MeSH data available.


Related in: MedlinePlus

Photomicrographs of a sagittally sectioned foot of a representative Balb/c mouse sacrificed 25 days following inoculation with L. major and treatment with AMB-ND. Panel A) Note the mild inflammation in subcutaneous tissue (arrows). The footpad epidermis (bottom) is intact and bone and muscle have no lesions. H&E, bar=500µm. Panel B). The mild focal inflammatory cell infiltrate consists of mixed mononuclear cells (arrows). Normal skeletal muscle lies beneath these cells with normal loose connective above. H&E, bar=500 µm.
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Figure 3: Photomicrographs of a sagittally sectioned foot of a representative Balb/c mouse sacrificed 25 days following inoculation with L. major and treatment with AMB-ND. Panel A) Note the mild inflammation in subcutaneous tissue (arrows). The footpad epidermis (bottom) is intact and bone and muscle have no lesions. H&E, bar=500µm. Panel B). The mild focal inflammatory cell infiltrate consists of mixed mononuclear cells (arrows). Normal skeletal muscle lies beneath these cells with normal loose connective above. H&E, bar=500 µm.

Mentions: In contrast to the PBS or empty ND treatment groups, AMB-ND treated mice manifested minimal change in footpad thickness throughout the experimental period. A small focus of footpad ulceration was present in 1 of 3 mice at day 25, with no ulceration in the other 2 mice. There was no ulceration in 3/3 mice at day 50. Histologic examination revealed that soft tissues of the feet had low numbers of L. major parasites and mild inflammation at day 25 PI. Inflammation became moderate by day 50. A photomicrograph of a sagittal section of a typical infected footpad from day 25 illustrates the mild nature of the inflammation (Figures 3A and 3B). Popliteal lymph nodes were moderately reactive and had low numbers of parasites, with mild neutrophil infiltration observed at days 25 and 50 PI. Livers of these mice had little or no inflammation at either day 25 or day 50 PI. Spleens and kidneys had no histologic lesions.


Effect of Amphotericin B Nanodisks on Leishmania major Infected Mice.

Cole P, Bishop J, Beckstead J, Titus R, Ryan R - Pharm Anal Acta (2014)

Photomicrographs of a sagittally sectioned foot of a representative Balb/c mouse sacrificed 25 days following inoculation with L. major and treatment with AMB-ND. Panel A) Note the mild inflammation in subcutaneous tissue (arrows). The footpad epidermis (bottom) is intact and bone and muscle have no lesions. H&E, bar=500µm. Panel B). The mild focal inflammatory cell infiltrate consists of mixed mononuclear cells (arrows). Normal skeletal muscle lies beneath these cells with normal loose connective above. H&E, bar=500 µm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4288788&req=5

Figure 3: Photomicrographs of a sagittally sectioned foot of a representative Balb/c mouse sacrificed 25 days following inoculation with L. major and treatment with AMB-ND. Panel A) Note the mild inflammation in subcutaneous tissue (arrows). The footpad epidermis (bottom) is intact and bone and muscle have no lesions. H&E, bar=500µm. Panel B). The mild focal inflammatory cell infiltrate consists of mixed mononuclear cells (arrows). Normal skeletal muscle lies beneath these cells with normal loose connective above. H&E, bar=500 µm.
Mentions: In contrast to the PBS or empty ND treatment groups, AMB-ND treated mice manifested minimal change in footpad thickness throughout the experimental period. A small focus of footpad ulceration was present in 1 of 3 mice at day 25, with no ulceration in the other 2 mice. There was no ulceration in 3/3 mice at day 50. Histologic examination revealed that soft tissues of the feet had low numbers of L. major parasites and mild inflammation at day 25 PI. Inflammation became moderate by day 50. A photomicrograph of a sagittal section of a typical infected footpad from day 25 illustrates the mild nature of the inflammation (Figures 3A and 3B). Popliteal lymph nodes were moderately reactive and had low numbers of parasites, with mild neutrophil infiltration observed at days 25 and 50 PI. Livers of these mice had little or no inflammation at either day 25 or day 50 PI. Spleens and kidneys had no histologic lesions.

Bottom Line: Balb/c and CH3 mice infected with Leishmania major on Day 0 were administered vehicle alone, empty ND or AMB-ND on Day 1 and day 7, via the tail vein.Mice were sacrificed 25 or 50 days post inoculation and tissue histology evaluated.It may be inferred that AMB-ND may be useful for prophylactic and/or treatment of early stage Leishmania spp. infection.

View Article: PubMed Central - HTML - PubMed

Affiliation: Microbiology, Immunology, and Pathology Department, Colorado State University, Fort Collins, CO 80523-1619.

ABSTRACT

Objective: To assess the efficacy of a novel formulation of the polyene antibiotic, amphotericin B (AMB), as therapy for cutaneous leishmaniasis in different mouse strains.

Methods: (AMB), was formulated into water-soluble transport particles, termed nanodisks (ND). Balb/c and CH3 mice infected with Leishmania major on Day 0 were administered vehicle alone, empty ND or AMB-ND on Day 1 and day 7, via the tail vein. Mice were sacrificed 25 or 50 days post inoculation and tissue histology evaluated. Balb/c mice treated with vehicle or empty ND showed signs of severe infection while CH3 mice had less inflammation and fewer parasites. AMB-ND treatment (2 mg/kg) had a marked therapeutic effect on L. major infected Balb/c mice and a discernable therapeutic benefit on CH3 mice.

Conclusions: AMB-ND is efficacious in the treatment of cutaneous leishmaniasis in both susceptible and resistant mouse strains. It may be inferred that AMB-ND may be useful for prophylactic and/or treatment of early stage Leishmania spp. infection.

No MeSH data available.


Related in: MedlinePlus