Nanotechnology approaches for delivery and targeting of Amphotericin B in fungal and parasitic diseases

Nanomedicine ◽  
2021 ◽  
Author(s):  
Mahboobeh Jafari ◽  
Samira Sadat Abolmaali ◽  
Ali Mohammad Tamaddon ◽  
Kamiar Zomorodian ◽  
Bahador Shahriarirad (Sarkari)
Keyword(s):  
Clinical Practice ◽  
Amphotericin B ◽  
Therapeutic Index ◽  
Fungal Diseases ◽  
Cross Resistance ◽  
Parasitic Diseases ◽  
Effective Strategy ◽  
The Subject ◽  
Lipid Formulations ◽  
Antimicrobial Potency

Amphotericin B (AMB), with widespread antifungal and anti-parasitic activities and low cross-resistance with other drugs, has long been identified as a potent antimicrobial drug. However, its clinical toxicities, especially nephrotoxicity, have limited its use in clinical practice. Lately, nano-based systems have been the subject of serious research and becoming an effective strategy to improve toxicity and antimicrobial potency. Commercial AMB lipid formulations have been developed in order to improve the therapeutic index and nephrotoxicity, while limited use is mainly due to their high cost. The review aimed to highlight the updated information on nanotechnology-based approaches to the development of AMB delivery and targeting systems for treatment of fungal diseases and leishmaniasis, regarding therapeutic challenges and achievements of various delivery systems.

scholarly journals Comparative Efficacies, Toxicities, and Tissue Concentrations of Amphotericin B Lipid Formulations in a Murine Pulmonary Aspergillosis Model

2006 ◽  
Vol 50 (6) ◽  
pp. 2122-2131 ◽  
Author(s):  
Jon A. Olson ◽  
Jill P. Adler-Moore ◽  
Julie Schwartz ◽  
Gerard M. Jensen ◽  
Richard T. Proffitt
Keyword(s):  
Amphotericin B ◽  
High Performance ◽  
Therapeutic Index ◽  
Pulmonary Aspergillosis ◽  
Lipid Complex ◽  
Drug Concentrations ◽  
Kidney Morphology ◽  
Amphotericin B Lipid Complex ◽  
Effective Use ◽  
Lipid Formulations

ABSTRACT Invasive aspergillosis, an important cause of morbidity and mortality in immunosuppressed (IS) patients, is often treated with amphotericin B lipid formulations. In the present study, liposomal amphotericin B (L-AMB) and amphotericin B lipid complex (ABLC) were compared in treatment of murine pulmonary aspergillosis. Uninfected, IS mice were treated for 4 days with 1, 4, 8, or 12 mg L-AMB or ABLC/kg of body weight, and their lungs were analyzed by high-performance liquid chromatography for drug concentrations. IS mice intranasally challenged with Aspergillus fumigatus were treated with 12, 15, or 20 mg/kg L-AMB or ABLC and monitored for survival, fungal burden (CFU), and tissue drug concentration. Blood urea nitrogen (BUN) levels and kidney histopathology were determined for uninfected and infected mice given 15 or 20 mg/kg L-AMB or ABLC. The results showed that both drugs had therapeutic levels of drug (>3.0 μg/g) in the lungs of uninfected or infected mice, and 24 h after the last dose, ABLC levels were significantly higher than L-AMB levels (P < 0.02). L-AMB and ABLC at 12 mg/kg both produced 57% survival, but only L-AMB at 15 or 20 mg/kg further increased survival to 80 to 90%, with BUN levels and kidney morphology similar to those of controls. Survival at 15 or 20 mg/kg ABLC was not significantly different than that of controls, and BUN levels were significantly elevated, with tubular alterations in uninfected animals and acute necrosis in kidney tubules of infected animals. In conclusion, although both drugs were effective in prolonging survival at 12 mg/kg, the reduced nephrotoxicity of L-AMB increased its therapeutic index, allowing for its safe and effective use at 15 or 20 mg/kg.

scholarly journals Carrier effects on biological activity of amphotericin B.

1996 ◽  
Vol 9 (4) ◽  
pp. 512-531 ◽  
Author(s):  
J Brajtburg ◽  
J Bolard
Keyword(s):  
Amphotericin B ◽  
Mammalian Cells ◽  
Fungal Infections ◽  
Therapeutic Index ◽  
Fungal Cell ◽  
Drug Of Choice ◽  
Higher Doses ◽  
Lipid Formulations

Amphotericin B (AmB), the drug of choice for the treatment of most systemic fungal infections, is marketed under the trademark Fungizone, as an AmB-deoxycholate complex suitable for intravenous administration. The association between AmB and deoxycholate is relatively weak; therefore, dissociation occurs in the blood. The drug itself interacts with both mammalian and fungal cell membranes to damage cells, but the greater susceptibility of fungal cells to its effects forms the basis for its clinical usefulness. The ability of the drug to form stable complexes with lipids has allowed the development of new formulations of AmB based on this property. Several lipid-based formulations of the drug which are more selective in damaging fungal or parasitic cells than mammalian cells and some of which also have a better therapeutic index than Fungizone have been developed. In vitro investigations have led to the conclusion that the increase in selectivity observed is due to the selective transfer of AmB from lipid complexes to fungal cells or to the higher thermodynamic stability of lipid formulations. Association with lipids modulates AmB binding to lipoproteins in vivo, thus influencing tissue distribution and toxicity. For example, lipid complexes of AmB can be internalized by macrophages, and the macrophages then serve as a reservoir for the drug. Furthermore, stable AmB-lipid complexes are much less toxic to the host than Fungizone and can therefore be administered in higher doses. Experimentally, the efficacy of AmB-lipid formulations compared with Fungizone depends on the animal model used. Improved therapeutic indices for AmB-lipid formations have been demonstrated in clinical trials, but the definitive trials leading to the selection of an optimal formulation and therapeutic regimen have not been done.

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.

A view on Practical Utility of Paradi Gunas

2017 ◽  
Vol 2 (2) ◽  
Author(s):  
Sachin Bagali ◽  
Umapati Baragi ◽  
M. R. Sajjanshetti
Keyword(s):  
Clinical Practice ◽  
Professional Practice ◽  
Continuous Process ◽  
Clinical Activity ◽  
Successful Management ◽  
Knowledge Domain ◽  
Practical Utility ◽  
The Subject ◽  
The Way

In the present day scenario prime need of Ayurveda is practical applicability of Ayurvedic fundamental principles and research should be more focused on all aspects where scientific inputs should confirm Ayurveda’s principles and philosophy. In Ayurveda, Gunas are described as the way of presentation of action without which no Karma (action) can be possible. Ayurveda has provided significance to every Guna so that they become useful in clinical practice. Clinical practice or research is a continuous process including a series of events which need to be performed in a sequential manner. Though there are many factors on which accomplishment of treatment depends, among these Charaka has given prime importance to Paradi Gunas. In clinical practice, Guna which are to be with Bhishak are mainly the Paradi Gunas which can also be called as miscellaneous Gunas. As rightly quoted by Acarya Charaka, for getting success in the treatment Paradi Gunas are the best. The Sutra quotes "Sidhyupaya Chikitsayam" which means that Chikitsa i.e. Dhatusamya will be done mainly with the help of Paradi Gunas. Knowledge of Paradi Gunas are required to be present in pharmacists, physicians and Researchers. Acharya Charaka says that Chikitsa Siddhi i.e. successful management of disease is not possible without the knowledge of Paradi Gunas. Paradi Gunas play an important role in selection, adaption and manifestation of drug as per condition of the disease and the patient in particular Desha and Kala. The ultimate goal of any clinical activity is to contribute in the knowledge domain and to improve professional practice. Thus this literary review of Paradi Gunas serves to explore the subject of the clinical practice.

scholarly journals Antitrypanosomal and Antileishmanial Activity of Chalcones and Flavanones from Polygonum salicifolium

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 175
Author(s):  
Ahmed M. Zheoat ◽  
Samya Alenezi ◽  
Ehab Kotb Elmahallawy ◽  
Marzuq A. Ungogo ◽  
Ali H. Alghamdi ◽  
...  
Keyword(s):  
Human Cell Line ◽  
Antileishmanial Activity ◽  
Cross Resistance ◽  
Future Research ◽  
Parasitic Diseases ◽  
Leishmania Mexicana ◽  
First Line ◽  
Trypanosoma Brucei Brucei ◽  
The Family

Trypanosomiasis and leishmaniasis are a group of neglected parasitic diseases caused by several species of parasites belonging to the family Trypansomatida. The present study investigated the antitrypanosomal and antileishmanial activity of chalcones and flavanones from Polygonum salicifolium, which grows in the wetlands of Iraq. The phytochemical evaluation of the plant yielded two chalcones, 2′,4′-dimethoxy-6′-hydroxychalcone and 2′,5′-dimethoxy-4′,6′-dihydroxychalcone, and two flavanones, 5,7-dimethoxyflavanone and 5,8-dimethoxy-7-hydroxyflavanone. The chalcones showed a good antitrypanosomal and antileishmanial activity while the flavanones were inactive. The EC50 values for 2′,4′-dimethoxy-6′-hydroxychalcone against Trypanosoma brucei brucei (0.5 μg/mL), T. congolense (2.5 μg/mL), and Leishmania mexicana (5.2 μg/mL) indicated it was the most active of the compounds. None of the compounds displayed any toxicity against a human cell line, even at 100 µg/mL, or cross-resistance with first line clinical trypanocides, such as diamidines and melaminophenyl arsenicals. Taken together, our study provides significant data in relation to the activity of chalcones and flavanones from P. salicifolium against both parasites in vitro. Further future research is suggested in order to investigate the mode of action of the extracted chalcones against the parasites.

Analysis of public safety in European countries

2015 ◽  
Vol 60 (8) ◽  
pp. 66-80
Author(s):  
Anna Wierzbicka ◽  
Agata Żółtaszek
Keyword(s):  
Quality Of Life ◽  
Public Safety ◽  
The State ◽  
Point Of View ◽  
European Countries ◽  
Effective Strategy ◽  
Sense Of Security ◽  
The Subject

Maintaining security is one of public tasks that determine the quality of life of the population. This issue is the subject of much debate both social and political. An in-depth assessment of the situation requires a variety of analyzes, significant from the point of view of the implementation of appropriate, effective strategy to increase the sense of security among citizens. The aim of the paper is to compare the state of public safety in selected European countries. The study was conducted based on Eurostat data from the years 2005–2011.

scholarly journals Evaluación del discurso narrativo en pacientes con daño cerebral leve

2012 ◽  
Vol 4 (3) ◽  
pp. 61
Author(s):  
Ana María Cachón
Keyword(s):  
Clinical Practice ◽  
Brain Injury ◽  
Single Case ◽  
Speech Analysis ◽  
Recovery Stage ◽  
Language Therapist ◽  
Speech Evaluation ◽  
Mild Brain Injury ◽  
Oral Speech ◽  
The Subject

In clinical practice there are few test that language therapist can use for the oral speech evaluation. The battery that has been frecuently used for the aphasia assessment, doesn´t usually give us this type of data, and when it happens, it is just a global description of the language of the subject, which doesn't make possible a detailed pursuit of the evolution. The relevance of linguistic production´s assessment becomes more evident in the study of patients with mild injury as well as when patient is in an advanced recovery stage. An assessment without a speech analysis uses to overestimate the subject's capacities and usually ends in an incomplete and inadequate intervention. The aim of the present work was to review different studies that include the narrative speech as part of the assessment, and to explore, with the study of a single case, some applications in this kind of studies for language evaluation in mild brain injury patients.

scholarly journals Boundary violation and sexual exploitation in psychiatry and psychotherapy: a review

2004 ◽  
Vol 10 (4) ◽  
pp. 312-320 ◽  
Author(s):  
Sameer P. Sarkar
Keyword(s):  
Health Care ◽  
Clinical Practice ◽  
Empirical Study ◽  
Sexual Exploitation ◽  
Professional Roles ◽  
Professional Boundaries ◽  
Boundary Violation ◽  
Psychotherapeutic Practice ◽  
The Subject ◽  
Sexual Boundary Violations

In psychiatric and psychotherapeutic practice, ‘boundaries' delineate the personal and the professional roles and the differences that should characterise the interpersonal encounters between the patient/client and the professional. Boundaries are essential to keep both parties safe. The author outlines the various types of boundary violation that can arise in clinical practice, their consequences (both clinical and legal), how professionals can avoid them and how health care institutions might respond, should they occur. He concentrates on sexual boundary violations, because these have been the subject of most empirical study.

scholarly journals Oral health promotion at Esperanza neighborhood, Corrientes

2021 ◽  
Vol 31 (3) ◽  
pp. 35-39
Author(s):  
AJ Encina-Tutuy ◽  
◽  
SE Martínez ◽  
CE Barrios ◽  
MS Dho ◽  
...  
Keyword(s):  
Health Promotion ◽  
Clinical Practice ◽  
Oral Health ◽  
Health Education ◽  
Oral Hygiene ◽  
Feeding Habits ◽  
Oral Health Promotion ◽  
National University ◽  
The Subject ◽  
The University

The subject Preventive Clinical Practice I of the Faculty of Dentistry of the National University of the Northeast developed the university extension project "Oral health Promotion atEsperanza neighborhood, Corrientes".The activities were donein the "Virgen de Itaty" primary school. Oral hygiene and healthy feeding habits were promoted, as well as providing dental servicesin field conditions to 63 students.The results obtained lead to the realization of new Promotion and Health Education activities, providing knowledge and tools in favor of the society.

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