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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 CH3 mouse sacrificed 25 days PI with L. mayor and treatment with PBS. Panel A) Moderate chronic inflammation is present in the soft tissues (arrows). The footpad epidermis and haired skin are intact. The inflammation has not spread to the bones. H&E, bar = 500 µm. Panel B) The subcutis has sheets of closely packed mixed mononuclear inflammatory cells with darkly stained lymphocytes and plasma cells in the upper half of the photomicrograph and more lightly stained macrophages in the lower half. These surround a central area of dense collagenous connective tissue. H&E, bar = 50 µm.
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Figure 2: Photomicrographs of a sagittally sectioned foot of a representative CH3 mouse sacrificed 25 days PI with L. mayor and treatment with PBS. Panel A) Moderate chronic inflammation is present in the soft tissues (arrows). The footpad epidermis and haired skin are intact. The inflammation has not spread to the bones. H&E, bar = 500 µm. Panel B) The subcutis has sheets of closely packed mixed mononuclear inflammatory cells with darkly stained lymphocytes and plasma cells in the upper half of the photomicrograph and more lightly stained macrophages in the lower half. These surround a central area of dense collagenous connective tissue. H&E, bar = 50 µm.

Mentions: Footpads of CH3 mice infected with L. major were moderately thickened at day 25 but not thickened at day 50. No footpad ulceration was observed, either on day 25 or day 50 PI. However, histologic examination of sagittal sections of infected feet revealed large numbers of L. Major parasites and moderate to severe inflammation in the soft tissues of the infected foot at day 25 (Figure 2A and 2B). By day 50 only a few organisms were present in mice treated with empty ND and none were detected in the PBS treatment group. At 50 days PI, mild inflammation was present in the soft tissues of the infected foot of mice in both treatment groups. The left popliteal lymph nodes of PBS treated mice had mildly reactively mphoid elements and mild neutrophil mild to days 25 and 50. Lymph nodes of mice treated with empty ND had mild to moderately reactive lymphoid elements and mild neutrophil infiltration at day 25, with moderate to severely reactive lymphoid elements and greater neutrophil infiltration at day 50. No L. major parasites were found in lymph nodes of infected CH3 mice. Likewise, spleens of infected CH3 mice treated with PBS or empty ND were unremarkable. Livers had mild inflammation at day 25 but none at day 50. CH3 mice had decreased numbers of organisms at day 50 compared to day 25 while Balb/c mice did not show this decrease. Furthermore, CH3 mice had less inflammation at days 25 and 50 than Balb/c mice.


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 CH3 mouse sacrificed 25 days PI with L. mayor and treatment with PBS. Panel A) Moderate chronic inflammation is present in the soft tissues (arrows). The footpad epidermis and haired skin are intact. The inflammation has not spread to the bones. H&E, bar = 500 µm. Panel B) The subcutis has sheets of closely packed mixed mononuclear inflammatory cells with darkly stained lymphocytes and plasma cells in the upper half of the photomicrograph and more lightly stained macrophages in the lower half. These surround a central area of dense collagenous connective tissue. H&E, bar = 50 µm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Photomicrographs of a sagittally sectioned foot of a representative CH3 mouse sacrificed 25 days PI with L. mayor and treatment with PBS. Panel A) Moderate chronic inflammation is present in the soft tissues (arrows). The footpad epidermis and haired skin are intact. The inflammation has not spread to the bones. H&E, bar = 500 µm. Panel B) The subcutis has sheets of closely packed mixed mononuclear inflammatory cells with darkly stained lymphocytes and plasma cells in the upper half of the photomicrograph and more lightly stained macrophages in the lower half. These surround a central area of dense collagenous connective tissue. H&E, bar = 50 µm.
Mentions: Footpads of CH3 mice infected with L. major were moderately thickened at day 25 but not thickened at day 50. No footpad ulceration was observed, either on day 25 or day 50 PI. However, histologic examination of sagittal sections of infected feet revealed large numbers of L. Major parasites and moderate to severe inflammation in the soft tissues of the infected foot at day 25 (Figure 2A and 2B). By day 50 only a few organisms were present in mice treated with empty ND and none were detected in the PBS treatment group. At 50 days PI, mild inflammation was present in the soft tissues of the infected foot of mice in both treatment groups. The left popliteal lymph nodes of PBS treated mice had mildly reactively mphoid elements and mild neutrophil mild to days 25 and 50. Lymph nodes of mice treated with empty ND had mild to moderately reactive lymphoid elements and mild neutrophil infiltration at day 25, with moderate to severely reactive lymphoid elements and greater neutrophil infiltration at day 50. No L. major parasites were found in lymph nodes of infected CH3 mice. Likewise, spleens of infected CH3 mice treated with PBS or empty ND were unremarkable. Livers had mild inflammation at day 25 but none at day 50. CH3 mice had decreased numbers of organisms at day 50 compared to day 25 while Balb/c mice did not show this decrease. Furthermore, CH3 mice had less inflammation at days 25 and 50 than Balb/c mice.

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