Linolenic acid-modified MPEG-PEI micelles for encapsulation of amphotericin B

2019 ◽  
Vol 11 (20) ◽  
pp. 2647-2662 ◽  
Author(s):  
Hongmei Xu ◽  
Fangfang Teng ◽  
Feilong Zhou ◽  
Li Zhu ◽  
Yi Wen ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Linolenic Acid ◽  
Water Solubility ◽  
Fungal Infections ◽  
Biofilm Inhibition ◽  
Comparable Activity ◽  
Reduced Toxicity

Aim: To encapsulate amphotericin B (AmB) with reduced toxicity and comparable activity. Results & methodology: The α-linolenic acid (ALA)-modified monomethoxy polyethylene glycol-g-PEI-g-ALA conjugate was employed to prepare AmB-loaded micelles (AmB-M). In vitro activity and release behavior of AmB-M were investigated. AmB-M enhanced AmB's water-solubility to 1.2 mg/ml, showing good storage stability. AmB-M could achieve a sustained and slow release of AmB, low hemolysis activity and negligible kidney toxicity when compared with commercial AmB injection. Antifungal activity and biofilm inhibition experiments confirmed that the antifungal activity of AmB-M against Candida albicans was similar to that of AmB injection. Conclusion: Monomethoxy polyethylene glycol-g-PEI-g-ALA micelles could be a preferable choice to treat systemic fungal infections as an efficient drug delivery system.

scholarly journals Amphotericin B-conjugated polypeptide hydrogels as a novel innovative strategy for fungal infections

2018 ◽  
Vol 5 (3) ◽  
pp. 171814 ◽  
Author(s):  
Chang Shu ◽  
Tengfei Li ◽  
Wen Yang ◽  
Duo Li ◽  
Shunli Ji ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Water Soluble ◽  
Naphthalene Acetic Acid ◽  
Innovative Strategy ◽  
Molecular Arrangement

The present work is focused on the design and development of novel amphotericin B (AmB)-conjugated biocompatible and biodegradable polypeptide hydrogels to improve the antifungal activity. Using three kinds of promoting self-assembly groups (2-naphthalene acetic acid (Nap), naproxen (Npx) and dexamethasone (Dex)) and polypeptide sequence (Phe-Phe-Asp-Lys-Tyr, FFDKY), we successfully synthesized the Nap-FFDK(AmB)Y gels, Npx-FFDK(AmB)Y gels and Dex-FFDK(AmB)Y gels. The AmB-conjugated hydrogelators are highly soluble in different aqueous solutions. The cryo-transmission electron microscopy and scanning electron microscopy micrographs of hydrogels afford nanofibres with a width of 20–50 nm. Powder X-ray diffraction analyses demonstrate that the crystalline structures of the AmB and Dex are changed into amorphous structures after the formation of hydrogels. Circular dichroism spectra of the solution of blank carriers and the corresponding drug deliveries further help elucidate the molecular arrangement in gel phase, indicating the existence of turn features. The in vitro drug releases suggest that the AmB-conjugated hydrogels are suitable as drug-controlled release vehicles for hydrophobic drugs. The antifungal effect of AmB-conjugated hydrogels significantly exhibits the antifungal activity against Candida albicans . The results of the present study indicated that the AmB-conjugated hydrogels are suitable carriers for poorly water soluble drugs and for enhancement of therapeutic efficacy of antifungal drugs.

scholarly journals Evaluation of bisphenylthiazoles as a promising class for combating multidrug-resistant fungal infections

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0258465
Author(s):  
Mohamed Hagras ◽  
Nader S. Abutaleb ◽  
Ahmed M. Sayed ◽  
Ehab A. Salama ◽  
Mohamed N. Seleem ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Antifungal Agent ◽  
Fungal Infections ◽  
Multidrug Resistant ◽  
Candida Auris ◽  
Conformationally Restricted ◽  
Normal Human

To minimize the intrinsic toxicity of the antibacterial agent hydrazinyloxadiazole 1, the hydrazine moiety was replaced with ethylenediamine (compound 7). This replacement generated a potent antifungal agent with no antibacterial activity. Notably, use of a 1,2-diaminocyclohexane moiety, as a conformationally-restricted isostere for ethylenediamine, potentiated the antifungal activity in both the cis and trans forms of N-(5-(2-([1,1’-biphenyl]-4-yl)-4-methylthiazol-5-yl)-1,3,4-oxadiazol-2-yl)cyclohexane-1,2-diamine (compounds 16 and 17). Both compounds 16 and 17 were void of any antibacterial activity; nonetheless, they showed equipotent antifungal activity in vitro to that of the most potent approved antifungal agent, amphotericin B. The promising antifungal effects of compounds 16 and 17 were maintained when assessed against an additional panel of 26 yeast and mold clinical isolates, including the Candida auris and C. krusei. Furthermore, compound 17 showed superior activity to amphotericin B in vitro against Candida glabrata and Cryptococcus gattii. Additionally, neither compound inhibited the normal human microbiota, and both possessed excellent safety profiles and were 16 times more tolerable than amphotericin B.

scholarly journals In Vitro Activity of Novel Antifungal Olorofim against Filamentous Fungi and Comparison to Eight Other Antifungal Agents

2021 ◽  
Vol 7 (5) ◽  
pp. 378
Author(s):  
Ourania Georgacopoulos ◽  
Natalie S. Nunnally ◽  
Eric M. Ransom ◽  
Derek Law ◽  
Mike Birch ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Fusarium Species ◽  
Geometric Mean ◽  
Treatment Options ◽  
Antifungal Susceptibility ◽  
Dihydroorotate Dehydrogenase ◽  
Drug Classes

Olorofim is a novel antifungal drug that belongs to the orotomide drug class which inhibits fungal dihydroorotate dehydrogenase (DHODH), thus halting pyrimidine biosynthesis and ultimately DNA synthesis, cell growth and division. It is being developed at a time when many invasive fungal infections exhibit antifungal resistance or have limited treatment options. The goal of this study was to evaluate the in vitro effectiveness of olorofim against a large collection of recently isolated, clinically relevant American mold isolates. In vitro antifungal activity was determined for 246 azole-susceptible Aspergillus fumigatus isolates, five A. fumigatus with TR34/L98H-mediated resistance, 19 Rhizopus species isolates, 21 Fusarium species isolates, and one isolate each of six other species of molds. Olorofim minimum inhibitory concentrations (MICs) were compared to antifungal susceptibility testing profiles for amphotericin B, anidulafungin, caspofungin, isavuconazole, itraconazole, micafungin, posaconazole, and voriconazole. Olorofim MICs were significantly lower than those of the echinocandin and azole drug classes and amphotericin B. A. fumigatus wild type and resistant isolates shared the same MIC50 = 0.008 μg/mL. In non-Aspergillus susceptible isolates (MIC ≤ 2 μg/mL), the geometric mean (GM) MIC to olorofim was 0.54 μg/mL with a range of 0.015–2 μg/mL. Olorofim had no antifungal activity (MIC ≥ 2 μg/mL) against 10% of the collection (31 in 297), including some isolates from Rhizopus spp. and Fusarium spp. Olorofim showed promising activity against A. fumigatus and other molds regardless of acquired azole resistance.

scholarly journals ANTIFUNGAL ACTIVITY OF THE ASSOCIATION OF CARVACROL WITH AMPHOTERICIN B OR WITH KETOCONAZOLE

2019 ◽  
Vol 16 (31) ◽  
pp. 12-17
Author(s):  
Gustavo Lima SOARES ◽  
Brenda Lavínia Calixto dos SANTOS ◽  
Brenna Ravena Araújo LUZ ◽  
Wylly Araújo de OLIVEIRA
Keyword(s):  
Antifungal Activity ◽  
Amphotericin B ◽  
Inhibitory Concentration ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Aspergillus Species ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Antifungal Action

Aspergillus species are a cause of a high number of fungal infections of difficult treatment, presenting an expressive number of deaths due to the complications in the severe cases of infection. The objective was to evaluate the antifungal action of carvacrol against Aspergillus species, as well as to evaluate the interactions when associated with amphotericin B or ketoconazole. The antifungal activity of carvacrol was evaluated by the broth microdilution method. The combinations of the substances were performed by the checkerboard methodology, to determine the Index of Fractional Inhibitory Concentration. Carvacrol showed antifungal activity against all Aspergillus strains used in the trials. In combinations of substances, only a combination of carvacrol and amphotericin B presented satisfactory results. Combinations of carvacrol and ketoconazole have not shown good. It is concluded that carvacrol is a good candidate for the antifungal drug because of its good activity against Aspergillus demonstrated in the present study, as well as in other studies in the literature. Their combination in vitro with amphotericin B or ketoconazole did not present any advantages over the use of antifungal drugs alone.

scholarly journals REFRACTORY FUNGAL VAGINITIS TREATED BY TOPICAL AMPHOTERICIN B. Review

2020 ◽  
Vol 16 (2) ◽  
pp. 55-58
Author(s):  
Falah Hasan Obayes AL-Khikani
Keyword(s):  
Antifungal Activity ◽  
Side Effects ◽  
Amphotericin B ◽  
Intravenous Injection ◽  
Fungal Infections ◽  
Wide Spectrum ◽  
Candida Spp

Vaginitis is a common problem for women regarding a worldwide health challenge with many side effects. Vaginitis is among the most visiting to gynecology clinics. About 75% of all reproductive women had at least one fungal vaginitis infection in their life, and more than 40% will have two or more than two.  Candida spp is the most prevalent in fungal vaginitis, while reports for unusual fungi were observed as mucor spp. Amphotericin B (AmB) belongs to the polyene group has a wide spectrum in vitro and in vivo antifungal activity. All of the known available formulas of AmB are administrated via intravenous injection to treat severe systemic fungal infections, while the development of the topical formula of AmB is still under preliminary development including topical vaginal AmB. Due to the revealing of antimicrobial-resistant fungi in recent years, this study explains the role of topical AmB in treating refractory fungi vaginitis that may not a response to other drugs reported in many cases that may help researchers to develop new effective formula of AmB regarding fungal vaginitis.

scholarly journals Influence of ascorbic acid and α-tocopherol on the autoxidation and in vitro antifungal activity of amphotericin B

2021 ◽  
Author(s):  
Mohammed Habib Belhachemi ◽  
Zahia Boucherit-Otmani ◽  
Kebir Boucherit ◽  
Sara Belmir
Keyword(s):  
Ascorbic Acid ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Morphological Changes ◽  
Reaction Medium ◽  
Thiobarbituric Acid ◽  
Cell Counting ◽  
Molecular Stability

Background and Purpose: Amphotericin B (AmB) is the standard treatment for systemic fungal infections; however, the formation of reactive oxygen species reduces the efficacy and stability of this molecule. The present study aimed to evaluate the effect of the combination of AmB with ascorbic acid and α-tocopherol on its autoxidation and antifungal activity. Materials and Methods: The antifungal activity against Candida albicans was evaluated by the viable cell counting method and checking their morphological changes with a scanning electron microscope. Monomer state of AmB was assessed by scanning the UV absorbance in the range of 300-450 nm and the lipid peroxidation was measured using quantification of thiobarbituric acid reactive-substances (TBARS). Results: Based on the findings, the addition of ascorbic acid (3×102 µg/mL) and α-tocopherol (16 µg/mL) to the reaction medium of AmB increased its antifungal activity while maintaining its molecular stability. Moreover, the level of TBARS formed in the reaction medium of AmB was significantly reduced after combination with ascorbic acid and α-tocopherol. Conclusion: Given their availability, their anti-free radical activity, and their low toxicity, the incorporation of ascorbic acid and α-tocopherol into the reaction medium of AmB seems to be a promising approach to obtain an effective antifungal formulation.

Smart Gn-Keto Nanohybrid Embedded Topical System for Effective Management of Dermatophytosis

2019 ◽  
Vol 9 (1) ◽  
pp. 21-28
Author(s):  
Nisha Sharma ◽  
Shashikiran Misra
Keyword(s):  
Antifungal Activity ◽  
Fungal Infections ◽  
High Surface ◽  
High Surface Area ◽  
Vital Role ◽  
Common Disease ◽  
Microdilution Method ◽  
Enhanced Solubility ◽  
Bioactive Agents

Background and Objectives: Dermatophytosis (topical fungal infection) is the 4th common disease in the last decade, affecting 20-25% world’s population. Patients of AIDS, cancer, old age senescence, diabetes, cystic fibrosis become more vulnerable to dermatophytosis. The conventional topical dosage proves effective as prophylactic in preliminary stage. In the advanced stage, the therapeutics interacts with healthy tissues before reaching the pathogen site, showing undesirable effects, thus resulting in pitiable patient compliance. The youngest carbon nano-trope “Graphene” is recently used to manipulate bioactive agents for therapeutic purposes. Here, we explore graphene via smart engineering by virtue of high surface area and high payload for therapeutics and developed graphene–ketoconazole nanohybrid (Gn-keto) for potent efficacy towards dermatophytes in a controlled manner. </P><P> Methods: Polymethacrylate derivative Eudragit (ERL100 and ERS 100) microspheres embedded with keto and Gn-keto nanohybrid were formulated and characterized through FTIR, TGA, and SEM. In vitro drug release and antifungal activity of formulated Gn-keto microspheres were assessed for controlled release and better efficacy against selected dermatophytes. </P><P> Results: Presence of numerous pores within the surface of ERL100 microspheres advocated enhanced solubility and diffusion at the site of action. Controlled diffusion across the dialysis membrane was observed with ERS100 microspheres owing to the nonporous surface and poor permeability. Antifungal activity against T. rubrum and M. canis using microdilution method focused on a preeminent activity (99.785 % growth inhibition) of developed nanohybrid loaded microspheres as compared to 80.876% of keto loaded microspheres for T. rubrum. The culture of M. canis was found to be less susceptible to formulated microspheres. Conclusion: Synergistic antifungal activity was achieved by nanohybrid Gn-Keto loaded microspheres against selected topical fungal infections suggesting a vital role of graphene towards fungi.

Antifúngicos poliénicos. Mecanismo de acción y aplicaciones

2020 ◽  
Vol 63 (2) ◽  
pp. 7-17
Author(s):  
Evelyn Rivera-Toledo ◽  
Alan Uriel Jiménez-Delgadillo ◽  
Patricia Manzano-Gayosso
Keyword(s):  
Antifungal Activity ◽  
Key Words ◽  
Secondary Metabolism ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Variable Number ◽  
Therapeutic Failure ◽  
Morbidity And Mortality ◽  
Clinical Use

The first compounds with specific antifungal activity were identified in the middle of the last century as a product of the secondary metabolism of bacteria of the order Actinomycetales, and their clinical use significantly diminished the morbidity and mortality associated with severe fungal infections. Many of such biosynthetic compounds are characterized by a chemical polygenic structure, with a variable number of carbon-carbon double bonds. Currently, besides polygenic antimycotics, there are other antifungal agents, such as the azole compounds, that have less toxicity in patients; however, cases of therapeutic failure with such compounds have been documented, therefore, the use of polygenics is still the best alternative in such cases. This review presents data about the properties and applications of antifungal-polygenic compounds using amphotericin B as a model. Key words: Amphotericin B; antifungal polyenes; ergosterol

Biodegradable polymers-based nanoparticles to enhance the antifungal efficacy of fluconazole against Candida albicans

2021 ◽  
Vol 22 ◽  
Author(s):  
Noha Saleh ◽  
Soha Elshaer ◽  
Germeen Girgis
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Encapsulation Efficiency ◽  
Water Solubility ◽  
In Vitro Release ◽  
Double Emulsion ◽  
Dilution Method ◽  
Ft Ir ◽  
Antifungal Efficacy

Background: Fluconazole (FLZ), a potent antifungal medication, is characterized by poor water solubility that reduced its antifungal efficacy. Objective: This study aimed to prepare FLZ-loaded polymeric nanoparticles (NPs) by using different polymers and techniques as a mean of enhancing the antifungal activity of FLZ. Methods: NP1, NP2, and NP3 were prepared by the double emulsion/solvent evaporation method using PLGA, PCL, and PLA, respectively. The ionotropic pre-gelation technique was applied to prepare an alginate/chitosan-based formulation (NP4). Particle size, zeta potential, encapsulation efficiency, and loading capacity were characterized. FT-IR spectra of FLZ, the polymers, and the prepared NPs were estimated. NP4 was selected for further in-vitro release evaluation. The broth dilution method was used to assess the antifungal activity of NP4 using a resistant clinical isolate of Candida albicans. Results: The double emulsion method produced smaller-sized particles (<390 nm) but with much lower encapsulation efficiency (< 12%). Alternatively, the ionic gelation method resulted in nanosized particles with a markedly higher encapsulation efficiency of about 40%. The FT-IR spectroscopy confirmed the loading of the FLZ molecules in the polymeric network of the prepared NPs. The release profile of NP4 showed a burst initial release followed by a controlled pattern up to 24 hours with a higher percent released relative to the free FLZ suspension. NP4 was able to reduce the value of MIC of FLZ by 20 times. Conclusion: The antifungal activity of FLZ against C. albicans was enhanced markedly via its loading in the alginate/chitosan-based polymeric matrix of NP4.

scholarly journals ANTI-CANDIDA ALBICANS ACTIVITY OF THE ASSOCIATION OF CITRONELAL WITH ANFOTERICIN B OR WITH CETOCONAZOLE

2019 ◽  
Vol 16 (31) ◽  
pp. 250-257
Author(s):  
Patrícia Duarte Costa SILVA ◽  
Brenda Lavínia Calixto dos SANTOS ◽  
Gustavo Lima SOARES ◽  
Wylly Araújo de OLIVEIRA
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Inhibitory Concentration ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Mortality Rates ◽  
New Drugs ◽  
High Morbidity ◽  
Isolated Species

Fungal infections caused by species of the genus Candida are responsible for high morbidity and mortality rates, mainly affecting immunocompromised individuals. Among fungi, Candida albicans is the most frequently isolated species of clinical specimens. A problem associated with increased resistance of pathogenic fungi to the agents used in the therapeutic regimen and the limited number of drugs to cure these infections. As a result, the search for new drugs with antifungal activity has become increasingly important. The aim of this study is to study the antifungal activity of citronellal alone and in combination with amphotericin B or ketoconazole. The Minimal Inhibitory Concentration of citronellal, amphotericin B and ketoconazole against strains of Candida albicans were evaluated by the microdilution technique, and the Minimum Fungicide Concentration of citronellal against the same strains was also performed. Through the checkerboard methodology the effect of the combination of citronelal with amphotericin B or with ketoconazole was determined. This study showed that the association of citronellal with ketoconazole was shown to be an additive against one of the strains of C. albicans and indifferent to another strain. While the combined activity of citronellal and amphotericin B demonstrated an indifferent effect on the strains tested.

Sign in / Sign up

Export Citation Format

Share Document