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New methods of delivery of amphotericin B
1Children's Hospital, Johannes Gutenberg University, Mainz, Germany.
Abstract:
Fungal infections continue to be a major problem in the management of immunocompromised patients. Despite its formidable toxicity and treatment failures, amphotericin B is still the drug of choice for most of these infections. One strategy for reducing the toxicity of amphotericin B and thus permitting administration of higher doses is that of using less toxic formulations. Entrapping amphotericin B into liposomes or binding it to other substances reduces its toxicity to host cells, whereas the selective binding of amphotericin B to ergosterol preserves its toxicity to fungal cells. Adding fungus-specific antibodies to such liposomes may further increase the efficiency of drug targeting. The initial unpublished data from controlled clinical trials of various liposomal preparations of amphotericin B are less encouraging than anticipated, but additional trials are needed for a proper evaluation. Another strategy for improving efficacy of amphotericin B is that of bringing it directly into contact with the body sites most likely to be infected. Intranasal delivery of amphotericin B for prevention of invasive aspergillosis has been evaluated in at least three different clinical trials with conflicting results; no controlled trials are available. Prophylactic administration of low doses of amphotericin B as an aerosol was the most effective of the regimens tested in an animal model of pulmonary aspergillosis and was also judged to be effective in a clinical trial using historical controls. Independent of the route of administration, in both an animal model was various clinical studies, early administration of amphotericin B was more effective than late administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
New amphotericin B formulations aim to reduce toxicity and improve efficacy for fungal infections in immunocompromised patients. Early administration and targeted delivery strategies show promise, though further trials are needed.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Fungal infections pose significant risks to immunocompromised patients.
- Amphotericin B remains a primary treatment despite toxicity and failure concerns.
Purpose of the Study:
- To explore strategies for reducing amphotericin B toxicity and enhancing its efficacy.
- To evaluate novel drug delivery methods for improved treatment outcomes.
Main Methods:
- Developing less toxic amphotericin B formulations, including liposomal preparations.
- Investigating targeted drug delivery via liposomes with antibodies.
- Assessing intranasal and aerosolized amphotericin B administration routes.
- Analyzing early versus late administration timing in animal models and clinical studies.
Main Results:
- Liposomal formulations aim to reduce host cell toxicity while preserving antifungal activity.
- Intranasal delivery for invasive aspergillosis prevention yielded conflicting results in trials.
- Aerosolized amphotericin B showed effectiveness in animal models and a historical control trial.
- Early administration of amphotericin B proved more effective than late administration across studies.
Conclusions:
- Novel amphotericin B formulations and delivery methods are crucial for managing fungal infections.
- Further clinical trials are necessary to validate the efficacy of liposomal preparations.
- Early and targeted administration strategies warrant continued investigation for improved patient care.