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Liposomal amphotericin b formulation

Mapi Fleury, Caroline Fonzo-Christe, Charline Normand, Pascal Bonnabry
A heavily immunosuppressed, 43-kg, 9-year-old patient was recovering from a bone marrow transplant. Primary prophylaxis against invasive fungal infections was liposomal amphotericin B (AmBisome(®), 2.3 mg/kg [100 mg] two times per week). Once home, following a first amphotericin B infusion, he presented with strong diarrhoea and vomiting; this was repeated after the second infusion. The clinical situation worsened rapidly and the patient was rehospitalised. On admission, he presented with acute renal failure...
December 2016: Drug Saf Case Rep
Pradyot Bhattacharya, Nahid Ali
Visceral leishmaniasis (VL) is one of the severest forms of parasite borne diseases worldwide with a mortality rate second only to malaria. Treatment of VL patients with currently available chemotherapeutic agents poses problems of large scale failure, toxicity, prolonged hospitalization time, high treatment cost and drug resistance. However, most of these problems can be overcome by the use of liposomal formulations of Amphotericin B (L-AmB). Of the two L-AmBs currently available in Indian market, AmBisome is imported and FUNGISOME is indigenous...
September 2016: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
Aline Raquel Voltan, Guillermo Quindós, Kaila P Medina Alarcón, Ana Marisa Fusco-Almeida, Maria José Soares Mendes-Giannini, Marlus Chorilli
Invasive mycoses are a major problem for immunocompromised individuals and patients in intensive care units. Morbidity and mortality rates of these infections are high because of late diagnosis and delayed treatment. Moreover, the number of available antifungal agents is low, and there are problems with toxicity and resistance. Alternatives for treating invasive fungal infections are necessary. Nanostructured systems could be excellent carriers for antifungal drugs, reducing toxicity and targeting their action...
2016: International Journal of Nanomedicine
Mohini Chaurasia, Pankaj K Singh, Anil K Jaiswal, Animesh Kumar, Vivek K Pawar, Anuradha Dube, Sarvesh K Paliwal, Manish K Chourasia
PURPOSE: To develop a biocompatible and bioresorbable calcium phosphate (CaP) nanoparticles (NPs) bearing Amphotericin B (AmB) with an aim to provide macrophage specific targeting in visceral leishmaniasis (VL). MATERIALS & METHODS: CaP-AmB-NPs were architectured through emulsion precipitation method. The developed formulation was extensively characterized for various parameters including in-vitro and in-vivo antileishmanial activity. Moreover, plasma pharmacokinetics, tissue biodistribution and toxicity profile were also assessed...
November 2016: Pharmaceutical Research
Koji Takemoto, Katsunori Kanazawa
Amphotericin B (AMPH-B) is a polyene antifungal agent with a superior and broad fungicidal spectrum, but its administration at a dose sufficient for treatment is difficult because of dose- and duration-dependent nephrotoxicity. To solve this dilemma, a liposomal formation of AMPH-B that achieved reduction of adverse effects while maintaining the efficacy, AmBisome® (L-AMB), was developed. In L-AMB, AMPH-B molecules are stabilized by phospholipids and cholesterol in the liposomal lipid bilayer, reducing the cytotoxicity for animal cells compared with that of the free-form AMPH-B...
June 21, 2016: Journal of Liposome Research
Shilpa N Patere, Pankaj O Pathak, Anil Kumar Shukla, Rajesh Kumar Singh, Vikash Kumar Dubey, Miten J Mehta, Anand G Patil, Vikram Gota, Mangal S Nagarsenker
Surface modification of liposomes with targeting ligands is known to improve the efficacy with reduced untoward effects in treating infective diseases like visceral leishmaniasis (VL). In the present study, modified ligand (ML), designed by modifying polysaccharide with a long chain lipid was incorporated in liposomes with the objective to target amphotericin B (Amp B) to reticuloendothelial system and macrophages. Conventional liposomes (CL) and surface modified liposomes (SML) were characterized for size, shape, and entrapment efficiency (E...
May 24, 2016: AAPS PharmSciTech
Neil R H Stone, Tihana Bicanic, Rahuman Salim, William Hope
Liposomal amphotericin B (AmBisome(®); LAmB) is a unique lipid formulation of amphotericin B. LAmB is a standard of care for a wide range of medically important opportunistic fungal pathogens. LAmB has a significantly improved toxicity profile compared with conventional amphotericin B deoxycholate (DAmB). Despite nearly 20 years of clinical use, the pharmacokinetics and pharmacodynamics of this agent, which differ considerably from DAmB, remain relatively poorly understood and underutilized in the clinical setting...
March 2016: Drugs
Jill P Adler-Moore, Jean-Pierre Gangneux, Peter G Pappas
Given the clinical success of commercial amphotericin B lipid products, investigators have begun making generic formulations of liposomal amphotericin B. Generic medicines are an attractive approach to help decrease the cost and accessibility to healthcare, provided that appropriate studies are performed to ensure bioequivalence with the parent product. This is of particular concern for liposomal drugs such as amphotericin B where liposomes are used as a carrier system to reduce the toxicity of the active agent...
March 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Ana Paula Perez, Maria Julia Altube, Priscila Schilrreff, Gustavo Apezteguia, Fabiana Santana Celes, Susana Zacchino, Camila Indiani de Oliveira, Eder Lilia Romero, Maria Jose Morilla
Aiming to improve the topical delivery of AmB to treat cutaneous fungal infections and leishmaniasis, ultradeformable liposomes containing amphotericin B (AmB-UDL) were prepared, and structural and functional characterized. The effect of different edge activators, phospholipid and AmB concentration, and phospholipid to edge activator ratio on liposomal deformability, as well as on AmB liposomal content, was tested. Liposomes having Tween 80 as edge activator resulted of maximal deformability and AmB/phospholipid ratio...
March 1, 2016: Colloids and Surfaces. B, Biointerfaces
José Ramón Azanza, Belén Sádada, Joana Reis
This article presents an overview of the characteristics of liposomes as drug carriers, particularly in relation to liposomal formulations of amphotericin B. General features regarding structure, liposome-cell interactions, stability, encapsulation of active substances and elimination of liposomes are described. Up to the present time extensive efforts to produce similar or bioequivalent products of amphotericin B formulations, in particular in the case of liposomal amphotericin B, have been unsuccessful in spite of having a very similar composition and even an apparently identical manufacturing process...
December 2015: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
Juan Pablo Botero Aguirre, Alejandra Maria Restrepo Hamid
BACKGROUND: The incidence of invasive fungal infections has increased globally as a result of several factors. Conventional amphotericin B (sodium deoxycholate) has been used as standard therapy for the treatment of invasive fungal infections; however, it is associated with adverse drug reactions, including acute kidney injury (AKI). New formulations of amphotericin B have aimed to improve the safety profile of the conventional formulation. OBJECTIVES: This review aimed to assess the effects of amphotericin B deoxycholate versus liposomal amphotericin B on kidney function...
2015: Cochrane Database of Systematic Reviews
Fernanda Cofré, Milena Villarroel, Loreto Castellón, María E Santolaya
The fungi of the order Mucorales cause mucormycosis, which usually presents as an invasive fungal disease with rapid angioinvasion in immunocompromised patients. Rhinocerebral is the most common presentation. The lipid formulations of amphotericin B are used as primary treatment in invasive mucormycosis; the combined use of posaconazole could allow a reduction in the dose of amphotericin B improving tolerance and adherence to treatment. Caspofungin and amphotericin B association has been shown to be synergistic in vitro and effective in murine models...
August 2015: Revista Chilena de Infectología: órgano Oficial de la Sociedad Chilena de Infectología
François Danion, Claire Aguilar, Emilie Catherinot, Alexandre Alanio, Susan DeWolf, Olivier Lortholary, Fanny Lanternier
Mucormycosis is a rare, though increasingly prevalent, life-threatening fungal disease caused by Mucorales. The incidence has increased over the last decade and its mortality remains high at around 50%. Mucormycosis occurs mostly in patients with diabetes mellitus and/or in the context of immunosuppression resulting from chemotherapy for hematological malignancy, hematopoietic stem cell transplantation, or solid-organ transplantation. In this situation, lung and rhino-orbito-cerebral infections are the most frequent localizations of the disease...
October 2015: Seminars in Respiratory and Critical Care Medicine
F Lanternier, S Poiree, C Elie, D Garcia-Hermoso, P Bakouboula, K Sitbon, R Herbrecht, M Wolff, P Ribaud, O Lortholary
BACKGROUND: Mucormycosis incidence is increasing and is associated with a high rate of mortality. Although lipid-based formulations of amphotericin B are the recommended first-line treatment, only one prospective trial in a limited number of patients has been performed to evaluate this regimen. METHODS: Patients with proven or probable mucormycosis were included between June 2007 and March 2011. Patients were scheduled to receive 10 mg/kg/day liposomal amphotericin B (L-AMB) monotherapy for 1 month and surgery was performed when appropriate...
November 2015: Journal of Antimicrobial Chemotherapy
Hung-Chang Hung, Gang-Yu Shen, Shiuan-Chih Chen, Kai-Jieh Yeo, Shih-Ming Tsao, Meng-Chih Lee, Yuan-Ti Lee
Pulmonary mucormycosis is commonly encountered in patients with diabetic ketoacidosis, hematologic malignancies, neutropenia, organ or hematopoietic stem cell transplantation, and malignancy, but it rarely occurs in high-risk patients with systemic lupus erythematosus (SLE). We present the case of a 40-year-old SLE female with fulminant pneumonia after remission of nephritis treated with rituximab, who developed severe pulmonary mucormycosis that led to her rapid death from acute respiratory failure and acute respiratory distress syndrome...
2015: Case Reports in Infectious Diseases
René Welte, Stephan Eschertzhuber, Stefan Weiler, Sandra Leitner-Rupprich, Maria Aigner, Cornelia Lass-Flörl, Eva Stienecke, Rosa Bellmann-Weiler, Michael Joannidis, Romuald Bellmann
Fungal cholangitis is a potentially life-threatening condition. As amphotericin B (AmB) has a broad antimycotic spectrum, in this study its biliary penetration and activity was determined in two patients treated with liposomal AmB (L-AmB) and in one patient receiving AmB colloidal dispersion (ABCD). Biliary and plasma AmB levels were quantified by high-performance liquid chromatography after purification by solid-phase extraction. For assessment of biliary AmB activity, isolates of Candida albicans, Candida tropicalis, Candida glabrata and Candida krusei were incubated in porcine bile at AmB concentrations of 0...
September 2015: International Journal of Antimicrobial Agents
Mohammad Asad, Pradyot Bhattacharya, Antara Banerjee, Nahid Ali
BACKGROUND: Visceral leishmaniasis (VL), a potentially fatal disease, is most prevalent in the Indian subcontinent, East Africa and South America. Since the conventional antileishmanial drugs have many limitations we evaluated a new ergosterol rich liposomal amphotericin B formulation, KALSOME™10 for its leishmanicidal efficacy, tolerability and immunomodulatory activity. METHODS: Normal healthy mice were treated with 3.5 mg/kg single and 7.5 mg/kg single and double doses of KALSOME™10...
2015: BMC Infectious Diseases
Justin Roberts, Josh Bingham, Alex C McLaren, Ryan McLemore
BACKGROUND: Liposomal amphotericin B is locally delivered to treat fungal orthopaedic infections but little is known about local tissue toxicity, if any, that might be associated with local delivery. QUESTIONS/PURPOSES: (1) Is liposomal amphotericin B cytotoxic in vitro? (2) Is locally delivered liposomal amphotericin B toxic to tissue in vivo? METHODS: Mouse fibroblasts (BA LB/3T3 A31) and osteoblasts (MC3T3) were exposed to two formulations of amphotericin B (liposomal and deoxycholate) at concentrations of 0, 1, 5, 10, 100, 500, and 1000 μg/mL...
July 2015: Clinical Orthopaedics and related Research
Victoria Leonhard, Roxana V Alasino, Ismael D Bianco, Ariel G Garro, Valeria Heredia, Dante M Beltramo
In this work a thorough characterization of the GM1 micelle-Amphotericin B (AmB) interaction was performed. The micelle formation as well as the drug loading occurs spontaneously, although influenced by the physicochemical conditions, pH and temperature. The chromatographic profile of GM1-AmB complexes at different molar ratios shows the existence of two populations. The differential absorbance of GM1, monomeric and aggregate AmB, allowed us to discriminate the presence of all of them in both fractions. Thus, we noted that at higher proportion of AmB in the complex, increases the larger population which is composed mainly of aggregated AmB...
2015: Current Drug Delivery
Zaid Al-Nakeeb, Vidmantas Petraitis, Joanne Goodwin, Ruta Petraitiene, Thomas J Walsh, William W Hope
Amphotericin B is a first-line agent for the treatment of invasive aspergillosis. However, relatively little is known about the pharmacodynamics of amphotericin B for invasive pulmonary aspergillosis. We studied the pharmacokinetics (PK) and pharmacodynamics (PD) of amphotericin B deoxycholate (DAMB), amphotericin B lipid complex (ABLC), and liposomal amphotericin B (LAMB) by using a neutropenic-rabbit model of invasive pulmonary aspergillosis. The study endpoints were lung weight, infarct score, and levels of circulating galactomannan and (1 → 3)-β-D-glucan...
May 2015: Antimicrobial Agents and Chemotherapy
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