Cited by 150Antifungal resistance and susceptibilityAdvanced Drug Delivery SystemsDrug Solubulity and Delivery Systems

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Efficacy of Oral Cochleate-Amphotericin B in a Mouse Model of Systemic Candidiasis

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Santangelo, Rosaria, Paderu, Padmaja, Delmas, Guillaume, Chen, Zi-Wei, Mannino, Raphael, Zarif, Leila, Perlin, David S.·2000·Antimicrobial Agents and Chemotherapy

DOI 10.1128/aac.44.9.2356-2360.2000PMC PMC90069

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Abstract

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.

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Zarif L. Segarra L. Jin T. Scolpino A. Hyra D. Perlin D. S. Graybill J. R. Mannino R. J. Oral and systemic delivery of AmB mediated by cochleates. AAPS PharmSci. 1 1999 S-453

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Authors: Santangelo, R., Paderu, P., Delmas, G., Chen, Z.-W., Mannino, R., Zarif, L., & Perlin, D. S.
Affiliations: Public Health Research Institute, New York, New York, 10016,1 and
BioDelivery Science Inc. UMDNJ, Newark, New Jersey 071032
ORCID: Santangelo, Rosaria
Paderu, Padmaja
Perlin, David S.
Venue: Antimicrobial Agents and Chemotherapy
Publisher: American Society for Microbiology
Published: 2000-09
Volume: 44
Issue: 9
Pages: 2356-2360
ISSN: 0066-4804 (ISSN-L)
1098-6596
DOI: 10.1128/aac.44.9.2356-2360.2000
PMC: PMC90069
OpenAlex: W2004315110
Cited by: 150
References: 44
Citations by year: 2026: 2 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 13 · 2021: 13 · 2020: 13 · 2019: 5 · 2018: 3 · 2017: 10 · 2016: 2 · 2015: 3 · 2014: 6 · 2013: 7 · 2012: 4
FWCI: 3.64
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Antimicrobial Agents and Chemotherapy (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
U.S. Public Health Service
National Institute of Allergy and Infectious Diseases (R43AI046040, R43-AI-46040)
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
Keywords: amphotericin B, cochleates, oral drug delivery, systemic candidiasis, Candida albicans, lipid-based drug delivery, antifungal therapy, mouse model
MeSH terms: Administration, Oral, Amphotericin B, Animals, Antifungal Agents, Candidiasis, Chemistry, Pharmaceutical, Delayed-Action Preparations, Disease Models, Animal, Drug Carriers, Female, Kidney, Lung, Mice, Inbred BALB C, Drug Delivery Systems, Treatment Outcome, Mice

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Efficacy of Oral Cochleate-Amphotericin B in a Mouse Model of Systemic Candidiasis

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