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[Treatment of experimental murine candidiasis with liposome-encapsulated amphotericin B]
Abstract:
Multilamellar liposomes composed of phosphatidyl choline, phosphatidic acid and cholesterol at a molar ratio of 4:1:4 were prepared so as to entrap a solution of amphotericin B (AMB) and its efficacy in the treatment of murine systemic candidiasis were studied. There were marked differences in susceptibility to systemic candidiasis among several strains of mice. The number of cultivable Candida albicans increased remarkably in the kidney up to 6.4 X 10(5) c.f.u./g, but not so marked in the lung, when challenged i.v. with 3.7 X 10(5) fungal cells into a relatively resistant strain BALB/C mice. Liposome-encapsulated amphotericin B (L-AMB) permitted larger doses of AMB to be administered without the occurrence of the acute anaphylaxis-like and subacute toxicity as expressed by a decreased renal function. The mice treated with a single injection of 4 mg/kg of L-AMB showed the prolonged survival after challenge. The results obtained showed that the use of liposomes as a drug delivery system for AMB would improve significantly the therapeutic efficacy of the antibiotic against candidiasis.
Insights
Liposome-encapsulated amphotericin B (L-AMB) offers improved treatment for systemic candidiasis in mice. This novel drug delivery system enhances therapeutic efficacy and reduces toxicity compared to conventional amphotericin B.
Area of Science:
- Pharmacology
- Drug Delivery Systems
- Mycology
Context:
- Systemic candidiasis is a serious fungal infection.
- Amphotericin B (AMB) is a primary antifungal agent but exhibits significant toxicity.
- Developing safer and more effective AMB formulations is crucial.
Purpose:
- To prepare multilamellar liposomes encapsulating amphotericin B (L-AMB).
- To evaluate the efficacy of L-AMB in treating murine systemic candidiasis.
- To assess the toxicity profile of L-AMB compared to free AMB.
Summary:
- Multilamellar liposomes containing phosphatidyl choline, phosphatidic acid, and cholesterol were formulated to encapsulate amphotericin B (AMB).
- Liposome-encapsulated amphotericin B (L-AMB) allowed for higher doses without acute anaphylaxis-like or subacute toxicity, such as decreased renal function.
- BALB/C mice treated with a single 4 mg/kg dose of L-AMB showed prolonged survival following intravenous challenge with Candida albicans.
Impact:
- Liposomes serve as an effective drug delivery system for amphotericin B.
- L-AMB significantly improves the therapeutic efficacy of amphotericin B against candidiasis.
- This approach holds promise for enhancing antifungal treatments with reduced side effects.