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Liposomal amphotericin b formulation

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https://www.readbyqxmd.com/read/28622334/sterol-14%C3%AE-demethylase-mutation-leads-to-amphotericin-b-resistance-in-leishmania-mexicana
#1
Roy Mwenechanya, Julie Kovářová, Nicholas J Dickens, Mudaliar Manikhandan, Pawel Herzyk, Isabel M Vincent, Stefan K Weidt, Karl E Burgess, Richard J S Burchmore, Andrew W Pountain, Terry K Smith, Darren J Creek, Dong-Hyun Kim, Galina I Lepesheva, Michael P Barrett
Amphotericin B has emerged as the therapy of choice for use against the leishmaniases. Administration of the drug in its liposomal formulation as a single injection is being promoted in a campaign to bring the leishmaniases under control. Understanding the risks and mechanisms of resistance is therefore of great importance. Here we select amphotericin B-resistant Leishmania mexicana parasites with relative ease. Metabolomic analysis demonstrated that ergosterol, the sterol known to bind the drug, is prevalent in wild-type cells, but diminished in the resistant line, where alternative sterols become prevalent...
June 16, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28490252/visceral-leishamiosis-in-immunocompromised-host-an-update-and-literature-review
#2
Pasquale Pagliano, Silvano Esposito
Visceral leishmaniasis (VL) is a chronic infectious disease endemic in tropical and sub-tropical areas including the Mediterranean basin, caused by a group of protozoan parasites of the genus Leishmania and transmitted by phlebotomine sandflies. Immunocompromised patients, in particular HIV positive, are considered at risk of VL. They report atypical signs and poor response to treatment due to impairment of T-helper and regulatory cells activity. Laboratory diagnosis is based on microscopy on bone marrow or spleen aspirates...
May 10, 2017: Journal of Chemotherapy
https://www.readbyqxmd.com/read/28480760/tissue-pharmacokinetics-and-pharmacodynamics-of-ambisome%C3%A2-l-ambis-in-uninfected-and-infected-animals-and-their-effects-on-dosing-regimens
#3
J P Adler-Moore, R T Proffitt, J A Olson, G M Jensen
By selecting a unique combination of lipids and amphotericin B, the liposome composition for AmBisome® (L-AmBis) has been optimized resulting in a formulation that is minimally toxic, targets to fungal cell walls, and distributes into and remains for days to weeks in various host tissues at drug levels above the MIC for many fungi. Procedures have been standardized to ensure that large scale production of the drug retains the drug's low toxicity profile, favorable pharmacokinetics and antifungal efficacy. Tissue accumulation and clearance with single or multiple intravenous administration is similar in uninfected and infected animal species, with tissue accumulation being dose-dependent and the liver and spleen retaining the most drug...
May 31, 2017: Journal of Liposome Research
https://www.readbyqxmd.com/read/28420334/mucormycosis-in-renal-transplant-recipients-review-of-174-reported-cases
#4
Yan Song, Jianjun Qiao, Gaffi Giovanni, Guangjun Liu, Hao Yang, Jianyong Wu, Jianghua Chen
BACKGROUND: Mucormycosis is a highly lethal fungal infection especially in immunocompromised individuals. METHODS: In order to review the epidemiology, diagnosis, and treatment of mucormycosis in renal transplant recipients we searched publications of mucormycosis cases in renal transplant recipients in PUBMED database up to December 2015. RESULTS: A total of 174 cases in renal transplant recipients were included in this review. Most of the cases (76%) were male...
April 18, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28339539/unique-aggregation-of-conjugated-amphotericin-b-and-its-interaction-with-lipid-membranes
#5
Sarah Kagan, Diana E Ickowicz, Abraham J Domb, Arie Dagan, Itzhack Polacheck
The purpose of this paper was to investigate the aggregation of amphotericin B (AMB) and AMB-arabinogalactan conjugate (AMB-AGC), and the interactions of these drugs with free and membrane-embedded sterols. Aggregation of AMB and AMB-AGC was studied by circular dichroic (CD) and UV absorbance spectroscopic techniques. The effect of liposomes on the spectra was utilized to investigate the interactions of aggregates with membrane-embedded sterols. Interaction with free sterols was studied by measuring sterols' effect on AMB/AMB-AGC susceptibility test...
June 1, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/28216467/nmr-and-esr-study-of-amphotericin-b-interactions-with-various-binary-phosphatidylcholine-phosphatidylglycerol-membranes
#6
J C Debouzy, L Mehenni, D Crouzier, M Lahiani-Skiba, G Nugue, M Skiba
Several biologically relevant phospholipids are considered as potential excipients for IV administration liposome's formulation of AMB (Biopharmaceututics Classification System Class IV). On the basis of in vivo bioavaibility studies, DMPC and DMPG were ranked as the first potent encapsulation enhancers for this model drug, especially if one expects to target DMPG rich systems as pulmonary surfactant. Subsequently, dispersions (multilayers) of DMPC, DMPG or in binary systems with various molar ratios were prepared with or without AMB (molar ratios AMB/lipid) and further investigated using the (1)H-,(31)P-NMR methods...
February 16, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28216150/novel-biodegradable-poly-gamma-glutamic-acid-amphotericin-b-complexes-show-promise-as-improved-amphotericin-b-formulations
#7
Tan Dinh, Qamar Zia, Swaleha Zubair, Paul Stapleton, Ruchi Singh, Mohammad Owais, Satyanarayana Somavarapu
Commercially available amphotericin B (AmB) formulations are limited by cytotoxicities, lower efficacies, shelf-life related issues and high production costs. In this study, AmB complexes based on poly(gamma-glutamic acid) (PGGA) were prepared and evaluated for their efficacies against AmB-deoxycholate (Fungizone(®)) and liposomal AmB (AmBisome(®)). Physical characterizations showed that AmB/PGGA complexes are nanoscopic (20-40 nm) with a negative zeta potential (-45.5 to -51.0 mV), water-soluble, stable in solution (up to 4 weeks, at 4 °C and 25 °C), and have a high drug loading (up to 35% w/w)...
February 16, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28191796/the-cost-of-treating-mucormycosis-with-isavuconazole-compared-with-standard-therapy-in-the-uk
#8
Emma Bagshaw, Daniel Kuessner, Jan Posthumus, Cesar Escrig, Michael Blackney, Sebastian Marcel Heimann, Oliver Andreas Cornely
AIM: Mucormycosis is a fungal infection associated with high mortality. Until recently, the only licensed treatments were amphotericin B (AMB) formulations. Isavuconazole (ISAV) is a new mucormycosis treatment. A UK-based economic model explored treatment costs with ISAV versus liposomal AMB followed by posaconazole. MATERIALS & METHODS: As a matched case-control analysis showed similar efficacy for ISAV and AMB, a cost-minimization approach was taken. Direct costs - drug acquisition, monitoring and administration, and hospitalization costs - were estimated from the National Health Service perspective...
February 13, 2017: Future Microbiology
https://www.readbyqxmd.com/read/28097002/ambisome-induced-avascular-necrosis-of-the-alae-of-the-nose-of-a-very-young-girl-suffering-from-kala-azar-a-case-report
#9
Shomik Maruf, Proggananda Nath, Fatima Aktar, Ariful Basher
Although liposomal amphotericin B (AmBisome) is considered as the first-line treatment for New Kala-azar, there is not enough evidence on the dosage formulation in children and its effect on them. Being considered as the safest drug for treatment of Kala-azar, this case of AmBisome-induced avascular necrosis now gives rise to the question; whether it is actually safe enough and if a dosage modification is needed in case of children. This so far, to the best of our knowledge, is the first instance of such severe adverse event due to AmBisome administration...
December 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28011960/visceral-leishmaniasis-in-immunocompromised-diagnostic-and-therapeutic-approach-and-evaluation-of-the-recently-released-idsa-guidelines
#10
Pasquale Pagliano, Tiziana Ascione, Giusy Di Flumeri, Giovanni Boccia, Francesco De Caro
Visceral Leishmaniasis (VL) is a chronic infectious disease endemic in tropical and sub-tropical areas including the Mediterranean basin, caused by a group of protozoan parasites of the genus Leishmania and transmitted by phlebotomine sandflies. Typically, VL is classified as a zoonotic infection when Leishmania infantum is the causative agent and as an anthroponotic one when L. donovani is the causative agent. Immunocompromised patients, in particular HIV positive, are considered at risk of VL. They may present atypical signs and poor response to the treatment due to a compromission of T-helper and regulatory cells activity...
December 1, 2016: Le Infezioni in Medicina
https://www.readbyqxmd.com/read/27878878/efficacy-and-safety-of-amphotericin-b-lipid-based-formulations-a-systematic-review-and-meta-analysis
#11
REVIEW
Laiza M Steimbach, Fernanda S Tonin, Suzane Virtuoso, Helena H L Borba, Andréia C C Sanches, Astrid Wiens, Fernando Fernandez-Llimós, Roberto Pontarolo
Invasive fungal infections, an important cause of mortality, are primarily treated using amphotericin B, which is available in different formulations, both conventional and lipid-based (liposomal, lipid complex, colloidal dispersion and Intralipid(®) infusion). The aim of our study was to determine the efficacy and safety of conventional amphotericin B vs its lipid-based formulations. A systematic review followed by pairwise meta-analysis was performed, including randomised controlled trials (RCTs) that evaluated the use of lipid-based amphotericin B in patients with any degree of immunosuppression and susceptibility to invasive fungal infection...
March 2017: Mycoses
https://www.readbyqxmd.com/read/27855062/safety-tolerability-and-pharmacokinetics-of-liposomal-amphotericin-b-in-immunocompromised-pediatric-patients
#12
Nita L Seibel, Aziza T Shad, Ihor Bekersky, Andreas H Groll, Corina Gonzalez, Lauren V Wood, Paul Jarosinski, Donald Buell, William W Hope, Thomas J Walsh
The safety, tolerability, and pharmacokinetics of the liposomal formulation of amphotericin B (L-AMB) were evaluated in 40 immunocompromised children and adolescents. The protocol was an open-label, sequential-dose-escalation, multidose pharmacokinetic study with 10 to 13 patients in each of the four dosage cohorts. Each cohort received daily dosages of 2.5, 5.0, 7.5, or 10 mg of amphotericin B in the form of L-AMB per kg of body weight. Neutropenic patients between the ages of 1 and 17 years were enrolled to receive empirical antifungal therapy or treatment of documented invasive fungal infections...
February 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27747684/confusion-between-two-amphotericin-b-formulations-leading-to-a-paediatric-rehospitalisation
#13
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 Safety—Case Reports
https://www.readbyqxmd.com/read/27605844/treatment-of-visceral-leishmaniasis-anomalous-pricing-and-distribution-of-ambisome-and-emergence-of-an-indigenous-liposomal-amphotericin-b-fungisome
#14
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
https://www.readbyqxmd.com/read/27540288/fungal-diseases-could-nanostructured-drug-delivery-systems-be-a-novel-paradigm-for-therapy
#15
REVIEW
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
https://www.readbyqxmd.com/read/27401407/bioinspired-calcium-phosphate-nanoparticles-featuring-as-efficient-carrier-and-prompter-for-macrophage-intervention-in-experimental-leishmaniasis
#16
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
https://www.readbyqxmd.com/read/27328721/ambisome-relationship-between-the-pharmacokinetic-characteristics-acquired-by-liposomal-formulation-and-safety-efficacy
#17
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...
July 15, 2016: Journal of Liposome Research
https://www.readbyqxmd.com/read/27222025/surface-modified-liposomal-formulation-of-amphotericin-b-in-vitro-evaluation-of-potential-against-visceral-leishmaniasis
#18
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
https://www.readbyqxmd.com/read/26818726/liposomal-amphotericin-b-ambisome-%C3%A2-a-review-of-the-pharmacokinetics-pharmacodynamics-clinical-experience-and-future-directions
#19
REVIEW
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
https://www.readbyqxmd.com/read/26768369/comparison-between-liposomal-formulations-of-amphotericin-b
#20
REVIEW
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
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