Liposomal formulations of amphotericin B: differences according to the scientific evidence (original) (raw)
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Indian Journal of Pharmaceutical Sciences, 2011
In the present study, we formulated long circulating liposomes for amphotericin B and characterized them. The formulation was optimized using 2 3 factorial designs. Pegylated liposomal formulation showed favorable results with reference to particle size (247.33±9.60 nm), percent entrapment efficiency (94.55±3.34%). TEM studies revealed that the liposomes were essentially spherical, hollow, and appeared like powder puff structures. From DSC study it was concluded that the pegylated formulation containing Amp B showed better stability and membrane integrity of the formulation. During the stability studies the formulation was found to be stable. When subjected to gamma scintigraphy kinetic tracer studies the formulation showed longer residence time in the blood in BALB/C mice.
Hemolytic and pharmacokinetic studies of liposomal and particulate amphotericin B formulations
Amphotericin B (AmB) is a very effective antifungal and antiparasitic drug with a narrow therapeutic window. To improve its efficacy/toxicity balance, new controlled release formulations have been developed based on different encapsulation systems, aggregation states and particle sizes modifications. The kinetics of the hemolytic process was studied not only to characterize the toxicity of different formulations but also as an indicator of drug release. Pharmacokinetic studies in beagle dogs were carried out with those formulations that exhibited the least hemolytic toxicity: liposomal formulation (AmBisome ® ), poly-aggregated AmB and encapsulated particulate AmB formulation. A novel poly-aggregated AmB formulation proved to be comparable in terms of low hemolytic activity with the marketed gold standard formulation: AmBisome ® . Its pharmacokinetic profile, characterized by a smaller area under the curve and larger volume of distribution, was markedly different from AmBisome ® , resulting in a cost-effective alternative for the treatment of leishmaniasis which can enhance the AmB passive target by the uptake by the cells of the reticulo-endothelial system. Effects of different variables such as type of formulation, dose, microencapsulation, anesthesia and dog's healthy state on AmB pharmacokinetics were studied.
Amphotericin B liposome preparation
Clinical Microbiology and Infectious Diseases, CMI, , 2008
ABSTRACT To reduce the in-vivo toxicity of the broad-spectrum antifungal drug amphotericin B, various lipid formulations of amphotericin B, ranging from lipid complexes to small unilamellar liposomes, have been developed and subsequently commercialised. These structurally diverse formulations differ in their serum pharmacokinetics as well as their tissue localisation, tissue retention and toxicity. These differences can affect the choice of formulation for a given infection, the time of initiation of treatment, and the dosing regimen. Although preclinical studies have shown similarities in the in-vitro and in-vivo antifungal activity of the formulations with comparable dosing, their acute and chronic toxicity profiles are not the same, and this has a significant impact on their therapeutic indices, especially in high-risk, immunosuppressed patients. With the recent introduction of new antifungal drugs to treat the increasing numbers of infected patients, the amphotericin B lipid formulations are now being studied to evaluate their potential in combination drug regimens. With proven efficacy demonstrated during the past decade, it is expected that amphotericin B lipid formulations will remain an important part of antifungal drug therapy.
Overview of the lipid formulations of amphotericin B
Journal of Antimicrobial Chemotherapy, 2002
Invasive fungal infections have been increasingly recognized as a major cause of morbidity and mortality in the immunocompromised host. Amphotericin B has a broad spectrum and has remained the drug of choice for life-threatening invasive fungal infections. However, adverse events, particularly renal insufficiency, are limiting factors in achieving an effective dose: the prescription of amphotericin B is a compromise between toxicity and efficacy. Lipid formulations offer a better therapeutic index by circumscribing amphotericin B toxicity. Three lipid formulations are available in most countries: AmBisome, the only true liposome; Abelcet, with a ribbon-like structure; and Amphocil/Amphotec, composed of disc-like structures. All these formulations contain amphotericin B, but they differ in shape, size, reticuloendothelial clearance, Cmax, AUC and visceral diffusion. The impact of these differences in pharmacokinetics and pharmacodynamics on clinical efficacy is still unclear. Efficac...
Acta bio-medica : Atenei Parmensis, 2012
Amphotericin B is a polyene macrolide derived from Streptomyces nodosus. Introduced into therapy in 1957, for decades amphotericin B has been the "gold standard" for fighting systemic fungal infections. In order to facilitate its systemic use, much attention has been paid to the development of pharmaceutical forms that could reduce its toxicity, especially for the kidney. Because of its low solubility in water and excellent solubility in lipids, amphotericin B is an ideal candidate for lipid-based formulations. Three different lipid formulations for intravenous infusion are currently commercially available: liposomal amphotericin (AmBisome), Amphotericin lipid complex (Abelcet) and Amphotericin colloidal dispersion (Amphocil). The three lipid formulations of amphotericin B show significantly different structural, physical, chemical, pharmacokinetic, pharmacodynamic and toxicological characteristics. Several lines of evidence indicate that the three formulations of amphoter...
Lipid formulations of amphotericin B: where are we today?
Journal de Mycologie Médicale / Journal of Medical Mycology, 2005
Amphotericin B deoxycholate (AmBD) was introduced 45 years ago for the treatment of invasive mycoses, on the basis of open-label non comparative data. Throughout these years of use it proved to be a life-saving drug but also a toxic compound which under current approval criteria might not meet licensing requirements. It still remains the gold standard of therapy for the broader spectrum of invasive mycoses, and exhibits the least potential for resistance. It is the drug used as comparator agent in clinical trials to test new antifungal agents. The three lipid based formulations of amphotericin B (LFABs) were created in an effort to overcome the toxicity of AmBD (nephrotoxicity and infusion related toxicity) and represent a significant advance in drug delivery technology. They have different physicochemical and pharmacokinetic properties, which have not yet found their clinical relevance. Clinically they have not proved more efficacious than the parent drug despite the advantage of administration in higher doses, but they have proved to be significantly less nephrotoxic. Few comparative studies of lipid products have been conducted. Liposomal amphotericin B (LAmB) is better tolerated with respect to infusion related events and can be infused in a shorter time. Amphotericin B colloidal dispersion (ABCD) has limited acceptance among clinicians because of the number of infusion related events. More head to head clinical trials are needed to check if one formulation is better than the others. Appropriate dosing is still open for LAmB and the role of LFABs as comparator drugs in clinical trials is emerging. The cost effectiveness of their use needs still remains to be demonstrated. In this paper, their role in combination antifungal therapy is investigated as well as new modes of administration (i.e. aerosolized).