scholarly journals Encochleated Amphotericin B: Is the Oral Availability of Amphotericin B Finally Reached?

2020 ◽  
Vol 6 (2) ◽  
pp. 66
Author(s):  
Maria Aigner ◽  
Cornelia Lass-Flörl
Keyword(s):  
Amphotericin B ◽  
The Novel ◽  
Phase Ii Clinical Trials ◽  
Wide Range ◽  
Life Threatening ◽  
Oral Availability ◽  
Reduced Toxicity ◽  
Yeasts And Molds ◽  
Lipid Formulations ◽  
Cargo Molecule

As the oldest and for many decades the only available agent for the treatment of life-threatening invasive fungal diseases, amphotericin B (AmB) is known for its broad-spectrum fungicidal activity against a wide range of yeasts and molds. However, the main drawback of the present formulations remains its toxicity, the limited use to intravenous administration, and the higher costs associated with the better tolerated lipid formulations. The novel nanoparticle-based encochleated AmB (CAmB) formulation encapsulates, protects, and delivers its cargo molecule AmB in the interior of a calcium-phospholipid anhydrous crystal. Protecting AmB from harsh environmental conditions and gastrointestinal degradation, CAmB offers oral availability in conjunction with reduced toxicity. Matinas BioPharma, Bedminster, NJ is on the way to develop CAmB named MAT2203, currently undergoing Phase II clinical trials.

scholarly journals Mucormycosis: the black fungus maiming COVID-19 patients in India

2021 ◽  
Vol 9 (8) ◽  
pp. 2535
Author(s):  
Priyanka Ghogre
Keyword(s):  
Developed Countries ◽  
The Novel ◽  
First Line ◽  
Airborne Spores ◽  
First Line Therapy ◽  
Disease Patterns ◽  
Line Therapy ◽  
Wide Range ◽  
Life Threatening ◽  
Lipid Formulations

The COVID-19 infection caused by the novel SARS-CoV-2 may be associated with a wide range of disease patterns, ranging from mild to life-threatening pneumonia. Mucormycosis is an emerging angioinvasive fungal infection caused by the ubiquitous filamentous fungi of the Mucorales order of the class of Zygomycetes. The prevalence of mucormycosis in India is about 80 times the prevalence in developed countries. Mucorales invade deep tissues via inhalation of airborne spores, percutaneous inoculation or ingestion. Rhino-orbito-cerebral form of mucormycosis is a relatively fatal infection and mortality rate rises to 50-85%. Extensive use of corticosteroids/monoclonal antibodies/broad-spectrum antibiotics may lead to the development/exacerbation of a preexisting fungal disease. Only amphotericin B and its lipid formulations and recently isavuconazole have been studied as first-line therapy for mucormycosis. On the contrary, posaconazole has been mainly studied as salvage therapy.

Preface

2002 ◽  
Vol 49 (suppl_1) ◽  
pp. 0iii-0iii
Author(s):  
Rosemary A. Barnes ◽  
Elizabeth M. Johnson ◽  
Frank C. Odds
Keyword(s):  
Amphotericin B ◽  
Fungal Infections ◽  
Editorial Office ◽  
Amphotericin B Deoxycholate ◽  
Patients At Risk ◽  
Life Threatening ◽  
Trade Names ◽  
General Aspects ◽  
Almost All ◽  
Lipid Formulations

Abstract The clinical problems caused by life-threatening, deeptissue fungal infections affect many different medical and surgical specialities where immunosuppression through disease or therapeutic advance has created a substantial sub-category of patients at risk of mycosis. Amphotericin B remains one of the first-line agents for treatment of almost all systemic mycoses, but the agent in its conventional deoxycholate formulation carries a serious penalty in terms of nephrotoxicity. Novel, lipid-associated formulations of amphotericin B have been introduced to combat the toxicity problem without loss of therapeutic efficacy. This supplement is based upon papers presented at an international symposium held in Australia on 8–9 July 2000. It focuses on AmBisome, a liposome-encapsulated formulation of amphotericin B, and draws together information on many general aspects of the diagnosis and treatment of deep tissue mycoses as well as providing a comprehensive set of reviews of all aspects of AmBisome —its pharmacology, toxicology, pharmacokinetics and clinical efficacy in a variety of mycoses and patient types. There is now considerably more clinical experience with lipid forms of amphotericin B than when the previous supplement on AmBisome was published by the Journal of Antimicrobial Chemotherapy in October 1999.1 Because the topic of the supplement is a formulation of an antifungal agent, not the agent itself, and because lipid-based formulations can vary in composition even when they are nominally prepared in the same way, we have taken the unusual step of referring to the various amphotericin B lipid formulations, and to ‘conventional’ amphotericin B-deoxycholate for injection, by their trade names. The editors would like to thank Christine Burley of the JAC Editorial Office, and Regine Buffels of Gilead Sciences for their untiring support and assistance in the preparation of this supplement. Reference 1. Speller, D. C. E. & Warnock, D. W. (Eds). (1991). Liposomal amphotericin B (AmBisome) in the treatment of systemic fungal infection. Journal of Antimicrobial Chemotherapy28, Suppl. B, 1–118.

Overview of the lipid formulations of amphotericin B

2002 ◽  
Vol 49 (suppl_1) ◽  
pp. 31-36 ◽  
Author(s):  
Bertrand Dupont
Keyword(s):  
Effective Dose ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Limiting Factors ◽  
Double Blind Study ◽  
Double Blind ◽  
Life Threatening ◽  
The Impact ◽  
Lipid Formulations

Abstract 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. Efficacy has been shown in neutropenic patients with fever of unknown origin, systemic candidosis, invasive aspergillosis, cryptococcal meningitis and a variety of other difficult-to-treat mycoses, such as Fusarium or Zygomycetes infections. The effective dose may vary from one formulation to the other and is c. 3–5 mg/kg/day. All formulations are less nephrotoxic than amphotericin B. In one randomized double-blind study, AmBisome 3 or 5 mg/kg/day was less nephrotoxic and gave fewer infusion-related events than Abelcet 5 mg/kg/day. Abelcet induces fewer infusion-related side effects than Amphocil. All formulations seem at least as effective as amphotericin B. In some patients with life-threatening mycosis who failed treatment with, or were intolerant to, amphotericin B, the lipid formulations were effective. Further studies with comparable selected high-risk patients are warranted to clarify the usefulness and the indications of each of the formulations. Cost is a factor limiting prescription in many institutions, where use is often restricted to patients intolerant of, or refractory to, amphotericin B.

scholarly journals In Vitro Activities of Posaconazole, Fluconazole, Itraconazole, Voriconazole, and Amphotericin B against a Large Collection of Clinically Important Molds and Yeasts

2006 ◽  
Vol 50 (6) ◽  
pp. 2009-2015 ◽  
Author(s):  
F. Sabatelli ◽  
R. Patel ◽  
P. A. Mann ◽  
C. A. Mendrick ◽  
C. C. Norris ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Fungal Pathogens ◽  
The Other ◽  
The Novel ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Large Collection ◽  
Time Intervals ◽  
Yeasts And Molds

ABSTRACT The in vitro activity of the novel triazole antifungal agent posaconazole (Noxafil; SCH 56592) was assessed in 45 laboratories against approximately 19,000 clinically important strains of yeasts and molds. The activity of posaconazole was compared with those of itraconazole, fluconazole, voriconazole, and amphotericin B against subsets of the isolates. Strains were tested utilizing Clinical and Laboratory Standards Institute broth microdilution methods using RPMI 1640 medium (except for amphotericin B, which was frequently tested in antibiotic medium 3). MICs were determined at the recommended endpoints and time intervals. Against all fungi in the database (22,850 MICs), the MIC50 and MIC90 values for posaconazole were 0.063 μg/ml and 1 μg/ml, respectively. MIC90 values against all yeasts (18,351 MICs) and molds (4,499 MICs) were both 1 μg/ml. In comparative studies against subsets of the isolates, posaconazole was more active than, or within 1 dilution of, the comparator drugs itraconazole, fluconazole, voriconazole, and amphotericin B against approximately 7,000 isolates of Candida and Cryptococcus spp. Against all molds (1,702 MICs, including 1,423 MICs for Aspergillus isolates), posaconazole was more active than or equal to the comparator drugs in almost every category. Posaconazole was active against isolates of Candida and Aspergillus spp. that exhibit resistance to fluconazole, voriconazole, and amphotericin B and was much more active than the other triazoles against zygomycetes. Posaconazole exhibited potent antifungal activity against a wide variety of clinically important fungal pathogens and was frequently more active than other azoles and amphotericin B.

scholarly journals Rhodotoruliosis: An Emerginag Opportunistic Mycosis of Humans and Animals

2021 ◽  
Vol 4 (2) ◽  
Author(s):  
Mahendra Pal
Keyword(s):  
Systemic Disease ◽  
Rhodotorula Glutinis ◽  
Source Of Infection ◽  
Direct Demonstration ◽  
Wide Range ◽  
Luxuriant Growth ◽  
Life Threatening ◽  
Household Environment ◽  
Mycotic Disease ◽  
Lipid Formulations

Rhodotoruliosis is an opportunistic emerging mycotic disease that affects both humans and animals. The source of infection is exogenous; and disease can occur in sporadic as well as epidemic form. The disease is caused by Rhodotorula, basidiomycetous yeast that lives as a saprophyte in the environment. Rhodotorula glutinis, R. mucilaginosa (R.rubra), and R. minuta are the most frequently encountered species of Rhodotorula. The species can be isolated from a wide range of sources in nature, including the soil, air, ocean, plants, dairy products, and the household environment. Fungemia, meningitis, ventriculitis, peritonitis, endocarditis, keratitis, endophtalmitis, hydrosalpinx, oral ulcer and lymphadenitis have all been linked to the fungus in humans. It causes skin infections in chicken, sea lion, and cat, lung infection in sheep, epididymitis in dog, and mastitis in cow and buffalo. The organism is an opportunist, taking advantage of immunosuppressive circumstances, indwelling devices, and antibiotic exposure. In order to confirm the diagnosis of rhodotoruliosis, laboratory assistance is required. The direct demonstration of Rhodotorula in the clinical specimens and its isolation in pure and luxuriant growth still considered the gold standard of diagnosis. Amphotericin B or one of its lipid formulations appears to be the medication of choice for treating the patient. The infection due to Rhodotorula especially in immunosuppressed individuals can be life threatening if the treatment is delayed. Prognosis of systemic disease in compromised subject may be grave. Early diagnosis is essential to start specific antifungal therapy of rhodotorulosiosis to prevent serious complications.

SARS-COV2 virus and Coronavirus disease (COVID-19)

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 977-982
Author(s):  
Mohamed J. Saadh ◽  
Bashar Haj Rashid M ◽  
Roa’a Matar ◽  
Sajeda Riyad Aldibs ◽  
Hala Sbaih ◽  
...  
Keyword(s):  
Close Contact ◽  
Antiviral Agents ◽  
Health Concern ◽  
The Novel ◽  
Global Public Health ◽  
Fatal Disease ◽  
Mild Disease ◽  
Life Threatening ◽  
Novel Coronavirus

SARS-COV2 virus causes Coronavirus disease (COVID-19) and represents the causative agent of a potentially fatal disease that is of great global public health concern. The novel coronavirus (2019) was discovered in 2019 in Wuhan, the market of the wet animal, China with viral pneumonia cases and is life-threatening. Today, WHO announces COVID-19 outbreak as a pandemic. COVID-19 is likely to be zoonotic. It is transmitted from bats as intermediary animals to human. Also, the virus is transmitted from human to human who is in close contact with others. The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is nearly supportive; the role of antiviral agents is yet to be established. The SARS-COV2 virus spreads faster than its two ancestors, the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. In this article, we aimed to summarize the transmission, symptoms, pathogenesis, diagnosis, treatment, and vaccine to control the spread of this fatal disease.

Nanoemulsions Loaded with Amphotericin B: Development, Characterization and Leishmanicidal Activity

2019 ◽  
Vol 25 (14) ◽  
pp. 1616-1622 ◽  
Author(s):  
Gabriela Muniz Félix Araújo ◽  
Gabriela Muniz Félix Araújo ◽  
Alana Rafaela Albuquerque Barros ◽  
Alana Rafaela Albuquerque Barros ◽  
João Augusto Oshiro-Junior ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Average Diameter ◽  
Isopropyl Myristate ◽  
Neglected Diseases ◽  
Clinical Form ◽  
Hydrophobic Compounds ◽  
Internal Phase ◽  
Oil In Water ◽  
Spherical Structures ◽  
Lipid Formulations

Leishmaniasis is one of the most neglected diseases in the world. Its most severe clinical form, called visceral, if left untreated, can be fatal. Conventional therapy is based on the use of pentavalent antimonials and includes amphotericin B (AmB) as a second-choice drug. The micellar formulation of AmB, although effective, is associated with acute and chronic toxicity. Commercially-available lipid formulations emerged to overcome such drawbacks, but their high cost limits their widespread use. Drug delivery systems such as nanoemulsions (NE) have proven ability to solubilize hydrophobic compounds, improve absorption and bioavailability, increase efficacy and reduce toxicity of encapsulated drugs. NE become even more attractive because they are inexpensive and easy to prepare. The aim of this work was to incorporate AmB in NE prepared by sonicating a mixture of surfactants, Kolliphor® HS15 (KHS15) and Brij® 52, and an oil, isopropyl myristate. NE exhibited neutral pH, conductivity values consistent with oil in water systems, spherical structures with negative Zeta potential value, monomodal size distribution and average diameter of drug-containing droplets ranging from 33 to 132 nm. AmB did not modify the thermal behavior of the system, likely due to its dispersion in the internal phase. Statistically similar antileishmanial activity of AmB-loaded NE to that of AmB micellar formulation suggests further exploring them in terms of toxicity and effectiveness against amastigotes, with the aim of offering an alternative to treat visceral leishmaniasis.

Reading Beyond the Code

2018 ◽  
Keyword(s):  
Relevance Theory ◽  
Literary Studies ◽  
The Novel ◽  
Human Communication ◽  
Communicative Acts ◽  
Face To Face ◽  
Code Model ◽  
Wide Range ◽  
Central Claim

This book explores the value for literary studies of relevance theory, an inferential approach to communication in which the expression and recognition of intentions plays a major role. Drawing on a wide range of examples from lyric poetry and the novel, nine of the ten chapters are written by literary specialists and use relevance theory both as an overall framework and as a resource for detailed analysis. The final chapter, written by the co-founder of relevance theory, reviews the issues addressed by the volume and explores their implications for cognitive theories of how communicative acts are interpreted in context. Originally designed to explain how people understand each other in everyday face-to-face exchanges, relevance theory—described in an early review by a literary scholar as ‘the makings of a radically new theory of communication, the first since Aristotle’s’—sheds light on the whole spectrum of human modes of communication, including literature in the broadest sense. Reading Beyond the Code is unique in using relevance theory as a prime resource for literary study, and is also the first to apply the model to a range of phenomena widely seen as supporting an ‘embodied’ conception of cognition and language where sensorimotor processes play a key role. This broadened perspective serves to enhance the value for literary studies of the central claim of relevance theory: that the ‘code model’ is fundamentally inadequate to account for human communication, and in particular for the modes of communication that are proper to literature.

scholarly journals Beehive Products as Antibacterial Agents: A Review

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 717
Author(s):  
Rita Abou Nader ◽  
Rawan Mackieh ◽  
Rim Wehbe ◽  
Dany El El Obeid ◽  
Jean Marc Sabatier ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Honey Bee ◽  
Antibacterial Agents ◽  
Royal Jelly ◽  
Biological Activities ◽  
Vital Role ◽  
Bee Venom ◽  
Bacterial Strains ◽  
Wide Range ◽  
Life Threatening

Honeybees are one of the most marvelous and economically beneficial insects. As pollinators, they play a vital role in every aspect of the ecosystem. Beehive products have been used for thousands of years in many cultures for the treatment of various diseases. Their healing properties have been documented in many religious texts like the Noble Quran and the Holy Bible. Honey, bee venom, propolis, pollen and royal jelly all demonstrated a richness in their bioactive compounds which make them effective against a variety of bacterial strains. Furthermore, many studies showed that honey and bee venom work as powerful antibacterial agents against a wide range of bacteria including life-threatening bacteria. Several reports documented the biological activities of honeybee products but none of them emphasized on the antibacterial activity of all beehive products. Therefore, this review aims to highlight the antibacterial activity of honey, bee venom, propolis, pollen and royal jelly, that are produced by honeybees.

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