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1.
Mycopathologia ; 189(2): 29, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483637

RESUMO

The emerging pathogen Trichophyton indotineae, often resistant to terbinafine (TRB), is known to cause severe dermatophytoses such as tinea corporis and tinea cruris. In order to achieve successful treatment for these infections, insight in the resistance profile of T. indotineae strains and rapid, reliable identification is necessary. In this research, a screening medium was tested on T. indotineae strains (n = 20) as an indication tool of TRB resistance. The obtained results were confirmed by antifungal susceptibility testing (AST) for TRB following the in vitro broth microdilution reference method. Additionally, AST was performed for eight other antifungal drugs: fluconazole, itraconazole, voriconazole, ketoconazole, griseofulvin, ciclopirox olamine, naftifine and amorolfine. Forty-five percent of the strains were confirmed to be resistant to terbinafine. The TRB resistant strains showed elevated minimal inhibitory concentration values for naftifine and amorolfine as well. DNA sequencing of the squalene epoxidase-encoding gene showed that TRB resistance was a consequence of missense point mutations in this gene, which led to amino acid substitutions F397L or L393F. MALDI-TOF MS was used as a quick, accurate identification tool for T. indotineae, as it can be challenging to distinguish it from closely related species such as Trichophyton mentagrophytes or Trichophyton interdigitale using morphological characteristics. While MALDI-TOF MS could reliably identify ≥ 95% of the T. indotineae strains (depending on the spectral library), it could not be used to successfully distinguish TRB susceptible from TRB resistant strains.


Assuntos
Alilamina/análogos & derivados , Antifúngicos , Arthrodermataceae , Terbinafina/farmacologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Trichophyton/genética , Arthrodermataceae/genética , Testes de Sensibilidade Microbiana , Farmacorresistência Fúngica/genética
2.
ACS Appl Bio Mater ; 6(11): 4714-4727, 2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37863908

RESUMO

Designing effective drug nanocarriers that are easy to synthesize, robust, and nontoxic is a significant challenge in nanomedicine. Polyamine-multivalent molecule nanocomplexes are promising drug carriers due to their simple and all-aqueous manufacturing process. However, these systems can present issues of colloidal instability over time and cellular toxicity due to the cationic polymer. In this study, we finely modulate the formation parameters of poly(allylamine-tripolyphosphate) complexes to jointly optimize the robustness and safety. Polyallylamine was ionically assembled with tripolyphosphate anions to form liquid-like nanocomplexes with a size of around 200 nm and a zeta potential of -30 mV. We found that nanocomplexes exhibit tremendous long-term stability (9 months of storage) in colloidal dispersion and that they are suitable as protein-loading agents. Moreover, the formation of nanocomplexes induced by tripolyphosphate anions produces a switch-off in the toxicity of the system by altering the overall charge from positive to negative. In addition, we demonstrate that nanocomplexes can be internalized by bone-marrow-derived macrophage cells. Altogether, these nanocomplexes have attractive and promising properties as delivery nanoplatforms for potential therapies based on the immune system activation.


Assuntos
Alilamina , Polifosfatos , Portadores de Fármacos , Polímeros
3.
Med Mycol ; 61(9)2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37562942

RESUMO

Adherence to antifungals is poor in high endemic regions where antifungal resistance is high. Poor readability of prescription/over-the-counter (OTC) antifungals may contribute to poor adherence, due to the patient not fully understanding the purpose, importance, and dosage of their antifungal medicine. As there are no reports on the readability of antifungals, this study examined the readability of patient-facing antifungal information. Antifungals (n = 16; five classes [allylamines, azoles, echinocandins, polyenes, and others-flucytosine and griseofulvin]) were selected. Readability of four sources of information, (i) summary of product characteristics, (ii) patient information leaflets (PILs), (iii) OTC patient information, and (iv) patient web-based information, was calculated using Readable software, to obtain readability scores [(i) Flesch Reading Ease [FRE], (ii) Flesch-Kinkaid Grade Level [FKGL], (iii) Gunning Fog Index, and (iv) Simple Measure of Gobbledygook (SMOG) Index) and text metrics [word count, sentence count, words/sentence, and syllables/word]. PILs, web-based resources, and OTC patient information had good readability (FRE mean ± sd = 52.8 ± 6.7, 58.6 ± 6.9, and 57.3 ± 7.4, respectively), just falling short of the ≥ 60 target. For FKGL (target ≤ 8.0), PILs, web-based resources, and OTC patient information also had good readability (mean ± sd = 8.5 ± 1.0, 7.2 ± 0.86, and 7.8 ± 0.1, respectively). Improved readability scores observed correlate with reduced words, words/sentence and syllables/word. Improving readability may lead to improved patient health literacy. Healthcare professionals, academics, and publishers preparing written materials regarding antifungals for the lay/patient community are encouraged to employ readability calculators to check the readability of their work, so that the final material is within recommended readability reference parameters, to support the health literacy of their patients/readers.


Yeast and mould infections can be difficult-to-treat, due to resistance. Our study shows that patient information on antifungals is fairly easy-to-read. Such information helps the patient know how best to take the medicine and help avoid resistance. Authors should always try to write clearly for patients.


Assuntos
Alilamina , Letramento em Saúde , Animais , Antifúngicos/uso terapêutico , Equinocandinas , Compreensão , Azóis , Polienos/uso terapêutico , Austrália , Reino Unido
4.
Curr Microbiol ; 80(9): 285, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37452917

RESUMO

Pigments produced by micro-organisms could contribute to their pathogenesis and resistance. The investigation into the red pigment of R. mucilaginosa and its ability to survive and resist has not yet been explored. This study aimed to investigate the survival and resistance of the R. mucilaginosa CQMU1 strain following inhibition of pigment production by naftifine and its underlying mechanism. The red-pigmented Rhodotorula mucilaginosa CQMU1 yeast was isolated from an infected toenail of a patient with onychomycosis. Cultivation of R. mucilaginosa in liquid and solid medium showed the effect of naftifine after treatment. Then, analysis of phagocytosis and tolerance to heat or chemicals of R. mucilaginosa was used to evaluate the survival and resistance of yeast to different treatments. Naftifine reversibly inhibited the pigmentation of R. mucilaginosa CQMU1 in solid and liquid media. Depigmented R. mucilaginosa CQMU1 showed increased susceptibility toward murine macrophage cells RAW264.7 and reduced resistance toward different types of chemicals, such as 1.5-M NaCl and 0.5% Congo red. Inhibition of pigment production by naftifine affected the survival and growth of R. mucilaginosa and its resistance to heat and certain chemicals. The results obtained could further elucidate the target of new mycosis treatment.


Assuntos
Alilamina , Rhodotorula , Humanos , Animais , Camundongos , Alilamina/farmacologia
5.
Anal Chim Acta ; 1271: 341474, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37328252

RESUMO

The determination of clinically significant amounts of tau protein in bodily fluids is a major problem in Alzheimer's disease (AD) diagnosis. As a result, the present work aims to develop a simple, label-free, fast, highly sensitive, and selective 2D carbon backbone graphene oxide (GO) patterned surface plasmon resonance (SPR) mediated affinity biosensor for Tau-441 monitoring. Initially, non-plasmonic nanosized GO was made using a modified Hummers' method, whereas green synthesized gold nanoparticles (AuNPs) were subjected to a layer-by-layer (LbL) design employing anionic and cationic polyelectrolytes. Several spectroscopical evaluations were carried out to ensure the synthesis of GO, AuNPs, and LbL assembly. Following that, the Anti-Tau rabbit antibody was immobilized on the designed LbL assembly using carbodiimide chemistry, and various studies such as sensitivity, selectivity, stability, repeatability, spiked sample analysis, etc., were conducted using the constructed affinity GO@LbL-AuNPs-Anti-Tau SPR biosensor. As an output, it shows a broad concentration range and a very low detection limit of 150 ng/mL to 5 fg/mL and 13.25 fg/mL, respectively. The remarkable sensitivity of this SPR biosensor represents the merits of a combination of plasmonic AuNPs and a non-plasmonic GO. It also exhibits great selectivity for Tau-441 in the presence of interfering molecules, which may be because of the immobilization of the Anti-Tau rabbit on the surface of the LbL assembly. Furthermore, it ensured high stability and repeatability, while spiked sample analysis and AD-induced animal samples analysis confirmed the practicability of GO@LbL-AuNPs-Anti-Tau SPR biosensor for Tau-441 detection. In conclusion, fabricated sensitive, selective, stable, label-free, quick, simple, and minimally invasive GO@LbL-AuNPs-Anti-Tau SPR biosensor will provide an alternative for AD diagnosis in the future.


Assuntos
Alilamina , Técnicas Biossensoriais , Grafite , Nanopartículas Metálicas , Animais , Coelhos , Ressonância de Plasmônio de Superfície/métodos , Ouro/química , Carbono , Proteínas tau , Nanopartículas em Multicamadas , Nanopartículas Metálicas/química , Técnicas Biossensoriais/métodos , Grafite/química
6.
J Assoc Physicians India ; 71(5): 11-12, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37355825

RESUMO

Dermatophytosis is a very common public health problem with high prevalence. Dermatophytes are a highly specialized set of filamentous fungi, which are adapted to keratinized tissues of humans and animals. Dermatophytosis is the most common fungal infection worldwide, affecting approximately 20-25% of the world's population. The etiological agents of dermatophytosis, called dermatophytes, change with geography and socioeconomic status. Trichophyton rubrum (T. rubrum) is the prime species for skin and nail infections followed by T. mentagrophytes/ T. interdigital complex. There is a shift from T. rubrum to T. mentagrophytes in India for superficial fungal infections. In order to deal with fungal infections, treatment strategies involve the use of systemic antifungals and/or topical antifungal agents. Naftifine is a synthetic allylamine antifungal first reported in 1974 and in 1985 became the first commercially available allylamine. The highly lipophilic nature of allylamine allows efficient penetration and reasonably high concentrations in the stratum corneum (SC) and hair follicles. Naftifine is fungicidal as well as fungistatic. The higher efficacy rates of allylamines over imidazoles for the treatment of fungal infections, even for months after cessation of treatment, is thought to be due to their fungicidal effect, as well as to potentially greater keratin binding and slower release from the SC. The effectiveness of naftifine is also demonstrated against various bacteria belonging to both gram-negative and gram-positive classes. The antiinflammatory property of naftifine has been reported in various preclinical studies where it has been shown to target the prostaglandin pathway. Naftifine 1 and 2% gel and cream is approved by The United States Food and Drug Administration (USFDA), recently naftifine has been approved in India by the Indian regulatory authority Drug Controller General of India (DCGI) for the treatment of dermatophytosis. Naftifine 2% also appears to be a promising treatment, requiring fewer applications than the 1% formulation. Naftifine appears to be effective in a single dose and has a shorter treatment duration than azoles. Naftifine demonstrated its efficacy and safety in various clinical studies of tinea infections. Naftifine offers a very useful and promising option for treating dermatophytosis.


Assuntos
Alilamina , Dermatomicoses , Tinha , Humanos , Alilamina/uso terapêutico , Alilamina/metabolismo , Pele , Dermatomicoses/tratamento farmacológico , Antifúngicos/uso terapêutico , Tinha/tratamento farmacológico , Tinha/metabolismo
7.
Int J Mol Sci ; 24(8)2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-37108491

RESUMO

Cellular membranes are essential for compartmentalization, maintenance of permeability, and fluidity in all three domains of life. Archaea belong to the third domain of life and have a distinct phospholipid composition. Membrane lipids of archaea are ether-linked molecules, specifically bilayer-forming dialkyl glycerol diethers (DGDs) and monolayer-forming glycerol dialkyl glycerol tetraethers (GDGTs). The antifungal allylamine terbinafine has been proposed as an inhibitor of GDGT biosynthesis in archaea based on radiolabel incorporation studies. The exact target(s) and mechanism of action of terbinafine in archaea remain elusive. Sulfolobus acidocaldarius is a strictly aerobic crenarchaeon thriving in a thermoacidophilic environment, and its membrane is dominated by GDGTs. Here, we comprehensively analyzed the lipidome and transcriptome of S. acidocaldarius in the presence of terbinafine. Depletion of GDGTs and the accompanying accumulation of DGDs upon treatment with terbinafine were growth phase-dependent. Additionally, a major shift in the saturation of caldariellaquinones was observed, which resulted in the accumulation of unsaturated molecules. Transcriptomic data indicated that terbinafine has a multitude of effects, including significant differential expression of genes in the respiratory complex, motility, cell envelope, fatty acid metabolism, and GDGT cyclization. Combined, these findings suggest that the response of S. acidocaldarius to terbinafine inhibition involves respiratory stress and the differential expression of genes involved in isoprenoid biosynthesis and saturation.


Assuntos
Alilamina , Sulfolobus acidocaldarius , Terbinafina/farmacologia , Terbinafina/metabolismo , Sulfolobus acidocaldarius/genética , Sulfolobus acidocaldarius/metabolismo , Alilamina/metabolismo , Glicerol/metabolismo , Lipídeos de Membrana/metabolismo , Archaea/genética
8.
Chem Pharm Bull (Tokyo) ; 71(2): 101-106, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36724973

RESUMO

Catalytic control of chemoselectivity is crucial in the synthesis of highly functionalized compounds. Although there are reports of efficient chemoselective reactions of alcohols and amines as nucleophiles, there are no reports of the chemoselective activation of alcohols and amines as electrophiles. In this study, highly O- and N-selective electrophilic activation of allylic alcohols and amines was achieved in Pd-catalyzed direct allylic alkylation. Allylamines were inherently more reactive than allylic alcohols (N-selectivity). On the other hand, the addition of catalytic amounts of 9-phenanthreneboronic acid preferentially activated allylic alcohols over allylamines (O-selectivity). Density functional theory (DFT) calculations suggested that the N-selectivity is due to the selective activation of allylic amines with ammonium cations, and boronate formation accelerates the activation of allylic alcohols.


Assuntos
Compostos Alílicos , Alilamina , Aminas , Paládio , Estrutura Molecular , Estereoisomerismo , Álcoois , Alquilação , Catálise
9.
Angew Chem Int Ed Engl ; 62(4): e202211631, 2023 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-36399016

RESUMO

Allylamines are important building blocks in the synthesis of bioactive compounds. The direct coupling of allylic C-H bonds and commonly available amines is a major synthetic challenge. An allylic C-H amination of 1,4-dienes has been accomplished by palladium catalysis. With aromatic amines, branch-selective allylic aminations are favored to generate thermodynamically unstable Z-allylamines. In addition, more basic aliphatic cyclic amines can also engage in the reaction, but linear dienyl allylic amines are the major products.


Assuntos
Compostos Alílicos , Alilamina , Aminação , Paládio/química , Compostos Alílicos/química , Aminas/química , Catálise
10.
Chem Commun (Camb) ; 59(2): 199-202, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36476727

RESUMO

A Rh-catalyzed C(sp2)-H propenylation has been reported by taking N-allyl benzimidazole as an allylamine congener. This transformation has been observed for the first time, where a tandem process of C-H allylation followed by alkene isomerization delivers a highly stereoselective trans-propenylated product. Detailed mechanistic studies including the characterization of rhodacycle-intermediates have been conducted to understand the mechanism.


Assuntos
Alilamina , Ródio , Ródio/química , Catálise , Alcenos/química
11.
Org Biomol Chem ; 21(1): 115-126, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36448662

RESUMO

A convenient and general protocol for the palladium-catalysed oxidation of internal allylamine derivatives to ß-amino ketones is reported. The transformation occurs at room temperature and shows a wide substrate scope as well as high functional group and N-protecting group tolerance. We also describe potential applications of the method, e.g., the synthesis of bioactive molecules or simple transformations of selected ß-amino ketones into other interesting building blocks.


Assuntos
Alilamina , Cetonas , Cetonas/química , Oxirredução , Paládio/química , Catálise
12.
Biomater Adv ; 143: 213184, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36371969

RESUMO

Herein, we report redox responsive, colon cancer targeting poly(allylamine) (PA)/eudragit S-100 (EU) nanoparticles (PAEU NPs) (≈59 nm). These disulfide crosslinked PAEU NPs are developed via air oxidation of thiolated PA and thiolated EU, eliminating the need of any external crosslinking agent for dual drug delivery. PAEU NPs can effectively encapsulate both hydrophilic doxorubicin (DOX) and hydrophobic curcumin (Cur) drug with ≈85 % and ≈97 % encapsulation efficiency respectively. Here, the combination of drugs having different anticancer mechanism offers the possibility of developing nanosystem with enhanced anticancer efficacy. The developed PAEU NPs show good colloidal stability and low drug release under physiological conditions, while high DOX (≈98 %) and Cur (≈93 %) release is observed in reducing environment (10 mM GSH). Further, DOX and Cur loaded PAEU NPs exhibit higher cancer cell killing efficiency as compared to individual free drugs. In vivo biodistribution studies with Balb/C mice display the retention of PAEU NPs in the colon region up to 24 h presenting the developed approach as an efficient way for colorectal cancer therapy.


Assuntos
Alilamina , Neoplasias Colorretais , Curcumina , Nanopartículas , Camundongos , Animais , Distribuição Tecidual , Doxorrubicina/uso terapêutico , Oxirredução , Neoplasias Colorretais/tratamento farmacológico
13.
Org Lett ; 24(37): 6783-6788, 2022 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-36074995

RESUMO

The cascade of Ir-catalyzed enantioselective allylic amination and Cu-catalyzed alkyne-azide cycloaddition was designed for the asymmetric synthesis of homoallylic amidines. The nucleophilic addition of an in situ-generated enantioenriched tertiary allylamine to a ketenimine intermediate triggers a rapid and stereospecific zwitterionic aza-Claisen rearrangement in a 1,3-chiral transfer manner. The approach allows modular access to enantioenriched α-chiral homoallylic amidines in high yields with a high level of enantiomeric purity.


Assuntos
Alilamina , Amidinas , Alcinos , Azidas , Catálise , Estrutura Molecular
14.
Anal Chem ; 94(40): 13820-13828, 2022 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-36170602

RESUMO

The interaction between polyamines and phosphate species is found in a wide range of biological and abiotic systems, yielding crucial consequences that range from the formation of supramolecular colloids to structure determination. In this work, the occurrence of phosphate-amino interactions is evidenced from changes in the electronic response of graphene field effect transistors (gFETs). First, the surface of the transistors is modified with poly(allylamine), and the effect of phosphate binding on the transfer characteristics is interpreted in terms of its impact on the surface charge density. The electronic response of the polyamine-functionalized gFETs is shown to be sensitive to the presence of different phosphate anions, such as orthophosphate, adenosine triphosphate, and tripolyphosphate, and a simple binding model is developed to explain the dependence of the shift of the Dirac point potential on the phosphate species concentration. Afterward, the impact of phosphate-amino interactions on the immobilization of enzymes to polyamine-modified graphene surfaces is investigated, and a decrease in the amount of anchored enzyme as the phosphate concentration increases is found. Finally, multilayer polyamine-urease biosensors are fabricated while increasing the phosphate concentration in the enzyme solution, and the sensing properties of the gFETs toward urea are evaluated. It is found that the presence of simple phosphate anions alters the nanoarchitecture of the polyelectrolyte-urease assemblies, with direct implications on urea sensing.


Assuntos
Alilamina , Técnicas Biossensoriais , Grafite , Trifosfato de Adenosina , Ânions , Grafite/química , Fosfatos , Poliaminas , Polieletrólitos , Transistores Eletrônicos , Ureia , Urease/química
15.
Expert Opin Pharmacother ; 23(12): 1363-1370, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35968655

RESUMO

INTRODUCTION: Low density Lipoprotein cholesterol)LDL-C) levels show a clear relationship with cardiovascular disease (CVD). Statins are first line agents to reduce LDL-C and CVD risk. However, combination lipid-lowering therapy is often required to achieve large reductions in LDL-C. AREA COVERED: Colesevelam HCl is a bile acid sequestrant (BAS), which reduces LDL-C by 16-22% in monotherapy and adds a further 12-14% reduction in LDL-C when combined with other lipid-lowering drugs. Like statins, colesevelam reduces C-reactive protein levels by 16% in monotherapy and additional 6% when added to statins. Colesevelam also reduced HbA1c by 4 mmol/mol (0.5%) when used alone and added to other hypoglycemic drugs in studies of patients with diabetes . EXPERT OPINION: Bile acid sequestrants reduce LDL-C and HbA1c and have some CVD outcome evidence. The uses of these agents are limited in patients with gastrointestinal disease or high triglycerides due to adverse effects on gut function and raising triglycerides and they interfere with the absorption of lipid-soluble drugs. Colesevelam has a higher bile acid binding capacity, and fewer adverse effects than other BAS. Colesevelam may be useful as a third line agent for treatment of hypercholesterolemia with some additional specific benefits on glycemic control.


Assuntos
Alilamina , Anticolesterolemiantes , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Hiperglicemia , Hiperlipidemias , Ácidos e Sais Biliares , LDL-Colesterol , Cloridrato de Colesevelam , Quimioterapia Combinada , Humanos , Hipolipemiantes , Triglicerídeos
16.
Dalton Trans ; 51(31): 11630-11640, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35861610

RESUMO

Salicylic acid (SA) is a phenolic phytohormone with critical roles in plant growth regulation and resistance to biotic and abiotic stress. Since low SA concentrations can modulate many plant biochemical responses, innovative analytical tools are required to deeply understand its activity and to control its exogenous application in modern agricultural systems. Herein, a NIR-activated composite based on NaYF4:Yb,Er@NaYF4 core@shell upconversion nanoparticles decorated with the poly(allylamine)-Cu(II) complex [UCNPs-PAAm-Cu(II)] was developed to sensitively determine the SA molecule in plant-derived samples. Accordingly, the PAAm-Cu(II) complex grafted on the UCNPs induces a strategic charge transfer band which triggers a quenching process through a resonance energy transfer (RET) mechanism. Such process is gradually deactivated upon the addition of SA and the consequent formation of the SA-Cu(II) complex, allowing a luminescence recovery in the 1-800 nM linear range. This mechanism is promoted by the strong stability of the SA-Cu(II) complex (log ß2-SA/Cu = 19.01) which is over twelve orders of magnitude stronger than the PAAm-Cu2+ counterpart. Furthermore, the equilibrium and kinetic studies on the involved mononuclear Cu2+ complexes formation permitted instantaneous analytical responses and excellent selectivity against other representative phytohormones and metallic cations. The reliability of this method was demonstrated by determining the SA content of some edible fruits and vegetables comprising apple, lemon, kiwi, tomato, and cucumber, whose concentrations ranged from 0.30 to 2.99 µg g-1, with percent recoveries between 94.6 to 102.3%. Thereby, the reported nanocomplex can help to understand the SA activity in plants with significant applications in crop yield improvement and food quality assessment.


Assuntos
Alilamina , Nanopartículas , Cobre , Cinética , Nanopartículas/química , Extratos Vegetais , Reguladores de Crescimento de Plantas , Reprodutibilidade dos Testes , Ácido Salicílico
17.
PLoS One ; 16(4): e0249628, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33826660

RESUMO

Cutaneous and mucocutaneous leishmaniasis affect a million people yearly, leading to skin lesions and potentially disfiguring mucosal disease. Current treatments can have severe side effects. Allylamine drugs, like terbinafine, are safe, including during pregnancy. This review assesses efficacy and safety of allylamines for the treatment of cutaneous and mucocutaneous leishmaniasis. It followed the PRISMA statement for reporting and was preregistered in PROSPERO(CRD4201809068). MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Global Health Library, Web of Science, Google Scholar, and clinical trial registers were searched from their creation to May 24th, 2020. All original human, animal, and in vitro studies concerning allylamines and cutaneous or mucocutaneous leishmaniasis were eligible for inclusion. Comparators-if any-included both placebo or alternative cutaneous or mucocutaneous leishmaniasis treatments. Complete cure, growth inhibition, or adverse events served as outcomes. The search identified 312 publications, of which 22 were included in this systematic review. There were one uncontrolled and two randomised controlled trials. The only well-designed randomised controlled trial that compared the treatment efficacy of oral terbinafine versus intramuscular meglumine antimoniate in 80 Leismania tropica infected patients showed a non-significant lower cure rate for terbinafine vs meglumine antimoniate (38% vs 53%). A meta-analysis could not be performed due to the small number of studies, their heterogeneity, and low quality. This systematic review shows that there is no evidence of efficacy of allylamine monotherapy against cutaneous and mucocutaneous leishmaniasis. Further trials of allylamines should be carefully considered as the outcomes of an adequately designed trial were disappointing and in vitro studies indicate minimal effective concentrations that are not achieved in the skin during standard doses. However, the in vitro synergistic effects of allylamines combined with triazole drugs warrant further exploration.


Assuntos
Alilamina/farmacologia , Leishmania/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Mucocutânea/tratamento farmacológico , Animais , Humanos , Leishmaniose Cutânea/parasitologia , Leishmaniose Mucocutânea/parasitologia , Prognóstico
18.
Drug Deliv ; 28(1): 343-356, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33517791

RESUMO

Tinea is a common superficial infection caused by keratinophylic fungi called dermatophytes. The objective of the current investigation was to develop and optimize a self-nanoemulsion drug delivery system (SENDDs) using clove oil loaded with naftifine (NF). Clove oil possesses good anti-inflammatory and antifungal properties that can support naftifine action. Box-Behnken designs were used to prepare plain and naftifine loaded SENDDs. The plain SENDDs were evaluated for their globule size. The medicated formulations (NF-CO-SENDDs) were characterized by measuring their globular size, ex vivo % NF permeated, level of interleukin-31 in rats, and antifungal activity. The optimum clove oil level was found to be 10-17%, while NF-CO-SENDDs formulations displayed globular sizes ranging from 119 to 310 nm. The statistical design confirmed the synergistic effect of clove oil and NF in the treatment of fungal infections, confirming that the anti-inflammatory effect of clove oil can counteract the side effects of NF. The optimized formulation composed of 14% clove oil, 12.5 mg Naftifine, and prepared with an Smix ratio equaling 3:1, exhibited good antifungal and anti-inflammatory activity, achieving up to 2-, 3-, 5.75-, and 2.74-fold increases in the amount of permeated NF, steady-state flux, permeability, and diffusion coefficients, respectively, compared with a commercial product. Moreover, the optimum formulation revealed an adequate zeta potential value of 28.31 ± 1.37 mV and showed reasonable stability with no or mild signs of skin sensitivity. Therefore, the designed nanoemulsions containing a combination of clove oil and naftifine could be considered promising delivery systems for the treatment of tinea.


Assuntos
Alilamina/análogos & derivados , Antifúngicos/farmacologia , Óleo de Cravo/farmacologia , Emulsões/farmacologia , Tinha/tratamento farmacológico , Administração Cutânea , Alilamina/farmacologia , Animais , Química Farmacêutica , Sistemas de Liberação de Medicamentos/métodos , Masculino , Nanopartículas/administração & dosagem , Tamanho da Partícula , Permeabilidade/efeitos dos fármacos , Ratos , Ratos Wistar , Pele/metabolismo , Absorção Cutânea/efeitos dos fármacos , Tensoativos/química
19.
Mater Sci Eng C Mater Biol Appl ; 119: 111428, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33321579

RESUMO

Development of a skin-targeted particulate delivery system providing an extended or sustained release of the payload and a localized therapeutic effect is one of the main challenges in the treatment of fungal skin infections. In the topical administration of antifungals, the drug should penetrate into the stratum corneum and lower layers of the skin in effective concentrations. Here, we introduce biodegradable calcium carbonate carriers containing 4.9% (w/w) of naftifine hydrochloride antimycotic allowing the efficient accumulation into the skin appendages. The proposed particulate formulation ensures the enhancement of the local drug concentration, prolongation of the payload release, and control over its rate. Furthermore, it provides a highly efficient cellular uptake and excellent bioavailability in vitro and enables a deep penetration during transfollicular delivery in vivo. The enhanced fungi growth inhibition efficiency of naftifine-loaded calcium carbonate carriers compared to naftifine solution makes them a promising alternative to creams and gels currently existing on the market.


Assuntos
Antifúngicos , Carbonato de Cálcio , Administração Cutânea , Alilamina/análogos & derivados , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Porosidade , Pele
20.
ACS Appl Mater Interfaces ; 12(45): 50581-50591, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33119264

RESUMO

Here, a novel poly(dimethylsiloxane) (PDMS)-based microbial culture system was investigated. Bacteria were encapsulated in functional and semipermeable membranes, mimicking the cell microenvironment and facilitating mass transport for interrogating microbial dynamics, thereby overcoming one of the major challenges associated with commercially available PDMS such as Sylgard 184. The hydrophobic nature and lack of control in the polymer network in Sylgard 184 significantly impede the the tunability of the transport and mechanical properties of the material as well as its usage as an isolation chamber for culturing and delivering microbes. Therefore, a novel PDMS composition was developed and functionalized with dimethylallylamine (DMAA) to alter its hydrophobicity and modify the polymer network. Characterization techniques including NMR spectroscopy, contact angle measurements, and sol-gel process were utilized to evaluate the physical and chemical properties of the newly fabricated membranes. Furthermore, the DMAA-containing polymer mixture was used as a proof of concept to generate hydrodynamically stable microcapsules and cultivate Escherichia coli cells in the functionalized capsules. The membrane exhibited a selective permeability to tetracycline, which diffused into the capsules to inhibit the growth of the encapsulated microbes. The functionality achieved here with the addition of DMAA, coupled with the high-throughput encapsulation technique, could prove to be an effective testing and diagnostic tool to evaluate microbial resistance, growth dynamics, and interspecies interaction and lays the foundation for in vivo models.


Assuntos
Alilamina/química , Técnicas de Cocultura , Dimetilpolisiloxanos/química , Escherichia coli/citologia , Dimetilpolisiloxanos/síntese química , Dispositivos Lab-On-A-Chip , Estrutura Molecular , Imagem Óptica , Tamanho da Partícula , Propriedades de Superfície
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