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Antimicrobial Agents and Chemotherapy, September 2000, p. 2356-2360, Vol. 44, No. 9
Public Health Research Institute, New York,
New York, 10016,1 and BioDelivery
Science Inc. UMDNJ, Newark, New Jersey
071032
Received 12 April 2000/Returned for modification 16 May
2000/Accepted 15 June 2000
Amphotericin B (AMB) remains the principal therapeutic choice for
deep mycoses. However, its application is limited by toxicity and a
route of administration requiring slow intravenous injection. An oral
formulation of this drug is desirable to treat acute infections and
provide prophylactic therapy for high-risk patients. Cochleates are a
novel lipid-based delivery system that have the potential for oral
administration of hydrophobic drugs. They are stable phospholipid-cation crystalline structures consisting of a spiral lipid
bilayer sheet with no internal aqueous space. Cochleates containing AMB
(CAMB) inhibit the growth of Candida albicans, and the in
vivo therapeutic efficacy of CAMB administered orally was evaluated in
a mouse model of systemic candidiasis. The results indicate that 100%
of the mice treated at all CAMB doses, including a low dosage of 0.5 mg/kg of body weight/day, survived the experimental period (16 days).
In contrast, 100% mortality was observed with untreated mice by day
12. The fungal tissue burden in kidneys and lungs was assessed in
parallel, and a dose-dependent reduction in C. albicans
from the kidneys was observed, with a maximum 3.5-log reduction in
total cell counts at 2.5 mg/kg/day. However, complete clearance of the
organism from the lungs, resulting in more than a 4-log reduction, was
observed at the same dose. These results were comparable to a
deoxycholate AMB formulation administered intraperitoneally at 2 mg/kg/day (P < 0.05). Overall, these data demonstrate
that cochleates are an effective oral delivery system for AMB in a
model of systemic candidiasis.
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Efficacy of Oral Cochleate-Amphotericin B in a
Mouse Model of Systemic Candidiasis
*
Corresponding author. Mailing address: Public Health
Research Institute, 455 First Ave., New York, NY 10016. Phone: (212) 578-0820. Fax: (212) 578-0804. E-mail: perlin{at}phri.org.
Antimicrobial Agents and Chemotherapy, September 2000, p. 2356-2360, Vol. 44, No. 9
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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