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Expert Opinion on Pharmacotherapy Aug 2003Amphotericin B spectrum covers most of the fungal pathogens involved in human diseases. Its use is limited by infusion-related effects and nephrotoxicity. As a result of... (Review)
Review
Amphotericin B spectrum covers most of the fungal pathogens involved in human diseases. Its use is limited by infusion-related effects and nephrotoxicity. As a result of strong lipophilic properties, encapsulation in liposomes or binding to lipid complexes led to the development of lipid formulations in an attempt to increase both efficacy and safety. Three lipid formulations of amphotericin B are commercially available: a liposomal preparation, a lipid complex and a colloidal dispersion. They differ in their lipid composition, shape, pharmacokinetic behaviour and clinical effects. The nephrotoxicity of these formulations is significantly decreased compared to their parent compound. Infusion-related events are lowest with liposomal amphotericin B. Increased efficacy of the lipid formulations over conventional amphotericin B, however, still has to be demonstrated. These formulations are mainly indicated for the treatment of documented fungal infections in patients failing conventional amphotericin B or with renal impairment. Liposomal amphotericin B is also indicated for empirical therapy of suspected fungal infections in febrile neutropenic patients giving this compound an advantage over the two other formulations. Lipid formulations of amphotericin B are extremely expensive. Whether the increase in cost translates into a long-term benefit for the patient is still unknown.
Topics: Amphotericin B; Animals; Antifungal Agents; Colloids; Excipients; Humans; Lipids; Liposomes; Mycoses
PubMed: 12877636
DOI: 10.1517/14656566.4.8.1277 -
Expert Opinion on Drug Delivery Feb 2024Amphotericin B (AmB), a promising antifungal and antileishmanial drug, acts on the membrane of microorganisms. The clinical use of AmB is limited due to issues... (Review)
Review
INTRODUCTION
Amphotericin B (AmB), a promising antifungal and antileishmanial drug, acts on the membrane of microorganisms. The clinical use of AmB is limited due to issues associated with its delivery including poor solubility and bioavailability, instability in acidic media, poor intestinal permeability, dose and aggregation state dependent toxicity, parenteral administration, and requirement of cold chain for transport and storage, etc.
AREAS COVERED
Scientists have formulated and explored various covalent conjugates of AmB to reduce its toxicity with increase in solubility, oral bioavailability, and payload or loading of AmB by using various polymers, lipids, carbon-based nanocarriers, metallic nanoparticles, and vesicular carriers, etc. In this article, we have reviewed various conjugates of AmB with polymers and nanomaterials explored for its delivery to give a deep insight regarding further exploration in future.
EXPERT OPINION
Covalent conjugates of AmB have been investigated by scientists, and preliminary and animal investigations have given successful results, which are required to be validated further with systematic investigation on safety and therapeutic efficacy in animals followed by clinical trials.
Topics: Animals; Amphotericin B; Antifungal Agents; Nanostructures; Polymers; Solubility; Drug Carriers
PubMed: 38243810
DOI: 10.1080/17425247.2024.2308073 -
Transplant Infectious Disease : An... Dec 1999Amphotericin B (amB) remains the gold standard for the treatment of invasive fungal infections. However, the efficacy is limited, with response rates from 10% to 80%.... (Comparative Study)
Comparative Study Review
Amphotericin B (amB) remains the gold standard for the treatment of invasive fungal infections. However, the efficacy is limited, with response rates from 10% to 80%. Moreover, amB is toxic, especially for the kidneys. New formulations have been developed in an attempt to improve both efficacy and tolerability. In an attempt to reduce toxicity, a number of investigators have reconstituted amB in a lipid emulsion, but few data are available on efficacy in documented infections. An improvement in immediate and renal tolerance was obtained with equivalent daily dose regimens, but the therapeutic index does not appear to be improved. This approach cannot be recommended at present. Three lipid formulations have been developed and are now available in most countries: amB colloidal dispersion (ABCD), amB lipid complex (ABLC), and liposomal amB (AmBisome). The efficacy of ABCD on various fungal infections has been assessed in open trials, with a response rate of 49% in aspergillosis, 70% in candidiasis, and 67% in mucormycosis. In two randomized trials comparing ABCD with amB in invasive aspergillosis and in persistent febrile neutropenia, the response rates were equivalent. ABCD was less nephrotoxic. In contrast, immediate reactions to ABCD were as frequent and severe as with amB. These immediate effects are more frequent during the first infusions and lessen as treatment continues. The recommended dose is 3-4 mg/kg/day. ABLC appeared to be effective as rescue therapy in various types of invasive mycoses, with a response rate of 42% in aspergillosis, 67% in candidiasis, and 82% in fusariosis. Efficacy identical to that of amB was demonstrated in a comparative randomized trial involving patients with invasive candidiasis. General and renal tolerability is improved compared with amB. The recommended dose regimen is 5 mg/kg/day. Liposomal amB (AmBisome) is the only truly liposomal formulation. The response rates in preliminary trials were 66% in aspergillosis and 81% in candidiasis. Several comparative studies have confirmed that this formulation has similar or superior efficacy relative to amB in various fungal infections and also in the empirical treatment of febrile neutropenia. Renal and general tolerability is excellent. The optimal dosing remains unclear but is generally between 3 and 5 mg/kg/day. A double-blind trial comparing the tolerance of liposomal amB and ABLC demonstrated that both infusion-related events and nephrotoxicity were significantly lower for liposomal amB. In sum, the new lipid formulations of amB are effective in various invasive fungal infections. The three formulations exhibit reduced nephrotoxicity compared with conventional amB. Large-scale comparative clinical trials may clarify issues of relative efficacy in various forms of mycotic infections.
Topics: Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Chemistry, Pharmaceutical; Drug Administration Schedule; Humans; Mycoses; Organ Transplantation; Postoperative Complications
PubMed: 11428998
DOI: 10.1034/j.1399-3062.1999.010406.x -
Clinical Pharmacokinetics Oct 1992Amphotericin B remains a very important drug for the treatment of fungal infections despite its toxicity. Encapsulation of amphotericin B into liposomes appears to... (Review)
Review
Amphotericin B remains a very important drug for the treatment of fungal infections despite its toxicity. Encapsulation of amphotericin B into liposomes appears to reduce the toxic effects and to improve the clinical efficacy, allowing higher dosages to be given. The exact mechanism behind the reduced toxicity is not yet known. Amphotericin B is widely distributed after intravenous administration as the deoxycholate solubilisate. The highest concentrations are found in the liver, spleen and kidney. Protein binding and binding to the tissues is very high. The fate of the drug in the body is not known in detail. Renal and biliary excretion are both low and no metabolites have been identified. The drug is still detectable in the liver, spleen and kidney for as long as 1 year after stopping therapy. The pharmacokinetics of the different liposomal amphotericin B or lipid complexes of amphotericin B, which were recently developed, are quite diverse. A number of these preparations, such as amphotericin B lipid complex (ABLC), 'AmBisome' and amphotericin B colloidal dispersion (ABCD) are in clinical development. Their pharmacokinetics depend to a large extent on the composition and particle size of the liposomes or lipid complexes. Relatively large structures such as ABLC are rapidly taken up by the mononuclear phagocyte system, whereas smaller liposomes remain in the circulation for prolonged periods. In all studies only the total amphotericin B (both free and liposome- or lipid-associated) concentrations were determined. There is a need for studies correlating clinical efficacy and tolerability of liposomal amphotericin B with the pharmacokinetic properties of these formulations.
Topics: Amphotericin B; Animals; Drug Administration Routes; Humans; Lipids; Liposomes; Pharmaceutical Vehicles; Tissue Distribution
PubMed: 1395361
DOI: 10.2165/00003088-199223040-00004 -
Dynamics (Pembroke, Ont.) 2001Amphotericin B is commonly used in the intensive care unit to treat invasive fungal infection. This medication is associated with a number of adverse events during... (Review)
Review
Amphotericin B is commonly used in the intensive care unit to treat invasive fungal infection. This medication is associated with a number of adverse events during infusion, such as fever, rigors, chills, electrolyte disorders and renal insufficiency. Liposomal amphotericin B can be used as an alternative to conventional amphotericin B to treat fungal infection. Patients receiving liposomal amphotericin B experience fewer adverse events than recipients of the conventional formulation; moreover, the liposomal formulation has been found to be as effective as the conventional amphotericin B to treat specific fungal infections. Unfortunately, the pharmacoeconomics of the liposomal formulation has limited the use of this medication. The purpose of this article is to present a brief summary of conventional amphotericin B with an emphasis on the narrow therapeutic index of this antibiotic. The liposomal amphotericin B solution is compared to conventional amphotericin B regarding the pharmacokinetics and pharmacodynamics. Therapeutic use, tolerability, and pharmacoeconomic implications of liposomal amphotericin B are discussed.
Topics: Amphotericin B; Antifungal Agents; Humans; Liposomes; Mycoses
PubMed: 11982230
DOI: No ID Found -
Biophysical Chemistry Dec 2021Amphotericin B, an acquainted antifungal drug, has reattracted the attention of most scholars due to its one important advantage of making the fungus less resistant....
Amphotericin B, an acquainted antifungal drug, has reattracted the attention of most scholars due to its one important advantage of making the fungus less resistant. Amphotericin B's antifungal properties are derived from its ability to interact with ergosterols on the fungal cells' membrane to form pores. However, the cholesterol in the human cell membranes is similar in structure to ergosterol, which cause the drug to produce certain toxicity and make the clinical use of amphotericin B limited. The study of the interaction between amphotericin B and lipid monolayer in the presence of cholesterol or ergosterol is crucial to understanding the mechanism of effect of the drug on cell membranes. Langmuir monolayer as a model for half of cell membranes can precisely control the proportion of components and the solution environment, which has been used to do a lot of research about the interaction of amphotericin B with lipids. It is noteworthy that some ions associated with life activities play an important role in it, such as calcium ions. In this work, the surface pressure-mean molecular area isotherms, elastic modulus and the surface pressure-time curves of DPPC/DOPC/sterol mixed monolayer with or without amphotericin B were studied in the different concentration of calcium ions. The morphology of the Langmuir-Blodgett films transferred on the mica were observed by atomic force microscopy. The results shown that AmB changed the elastic modulus and surface morphology of DPPC/DOPC/sterol mxied monolayer, which was significantly different with different types of sterols. Calcium ions can regulate the effect of this drug, which was clearly different due to different types of sterols. This work provides useful information to further understand the influence mechanism of calcium ions on the interaction between AmB and phospholipid/sterol monolayer, which is helpful to find out the effect mechanism of calcium ion on the interaction between AmB and phospholipid monolayer containing ergosterol or cholesterol and to understand the mechanism of AmB influencing on the membrane of fungal or human cells.
Topics: Amphotericin B; Calcium; Humans; Ions; Phosphatidylcholines; Sterols
PubMed: 34649214
DOI: 10.1016/j.bpc.2021.106695 -
Journal of Liposome Research Sep 2017AmBisome (liposomal amphotericin B) is among the earliest approved liposomal therapeutics, and has been in commercial use since the early 1990s. This review provides... (Review)
Review
AmBisome (liposomal amphotericin B) is among the earliest approved liposomal therapeutics, and has been in commercial use since the early 1990s. This review provides examples of non-clinical, regulatory, clinical label expansion, adverse event management, and supply chain control reflecting the real world challenges of a commercial liposomal therapeutic. We review examples of post-approval clinical development in severe lung infections, development of US and European guidance documents around liposomal therapeutics, the creation of a suitable placebo for blinded clinical trials, response to findings of a possible new category of adverse event (what turned out to be pseudohyperphosphatemia), challenges in handling the finished product in a setting with high risk of exposure of the product to temperatures outside of the established label storage conditions, and elements of continuingly increased aseptic processing requirements for manufacturing.
Topics: Amphotericin B; Antifungal Agents; Drug Stability; Humans; Liposomes; Temperature
PubMed: 28967274
DOI: 10.1080/08982104.2017.1380664 -
Therapeutic Delivery Jan 2013
Topics: Administration, Oral; Amphotericin B; Antifungal Agents; Chemistry, Pharmaceutical; Nanoparticles
PubMed: 23401912
DOI: 10.4155/tde.12.134 -
Molecules (Basel, Switzerland) Jun 2023Amphotericin B is a popular antifungal antibiotic, and despite decades of pharmacological application, the exact mode of its biological activity is still a matter of...
Amphotericin B is a popular antifungal antibiotic, and despite decades of pharmacological application, the exact mode of its biological activity is still a matter of debate. Amphotericin B-silver hybrid nanoparticles (AmB-Ag) have been reported to be an extremely effective form of this antibiotic to combat fungi. Here, we analyze the interaction of AmB-Ag with cells with the application of molecular spectroscopy and imaging techniques, including Raman scattering and Fluorescence Lifetime Imaging Microscopy. The results lead to the conclusion that among the main molecular mechanisms responsible for the antifungal activity of AmB is the disintegration of the cell membrane, which occurs on a timescale of minutes.
Topics: Amphotericin B; Anti-Bacterial Agents; Silver; Antifungal Agents; Cell Membrane; Nanoparticles; Candida albicans
PubMed: 37375242
DOI: 10.3390/molecules28124687 -
Current Pharmaceutical Design 2017Amphotericin B (AmB) is the drug of choice in the treatment of invasive fungal infections and visceral leishmaniasis. Although AmB has a higher selectivity for... (Review)
Review
Amphotericin B (AmB) is the drug of choice in the treatment of invasive fungal infections and visceral leishmaniasis. Although AmB has a higher selectivity for ergosterol (present in fungi and Leishmania spp. membrane) than for cholesterol, mammalian cells are affected by AmB, mainly in its oligomeric aggregated form, resulting in side effects, especially nephrotoxicity. The development of nanotechnology-based drug delivery systems for AmB is a promising avenue since nanoparticles have the ability to target drugs to the infected cells, and their prolonged drug release profile permits longer contact between the drug and the fungi/parasite. In this review, we made an overview about nanoparticles as colloidal carriers for AmB, including polymeric-based nanoparticles, protein-based nanoparticles and solid lipid-based nanoparticles with respect to their application for the treatment of invasive fungal infections and leishmaniasis.
Topics: Amphotericin B; Animals; Colloids; Drug Carriers; Drug Delivery Systems; Humans; Leishmaniasis; Mycoses; Nanoparticles; Nanotechnology
PubMed: 27799043
DOI: 10.2174/1381612822666161027103640