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1.
JMIRx Med ; 5: e51787, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38606668

RESUMO

Background: Animal-assisted therapy, also known as pet therapy, is a therapeutic intervention that involves animals to enhance the well-being of individuals across various populations and settings. Objective: This systematic study aims to assess the outcomes of animal-assisted therapy interventions and explore the associated policies. Methods: A total of 16 papers published between 2015 and 2023 were selected for analysis. These papers were chosen based on their relevance to the research topic of animal-assisted therapy and their availability in scholarly databases. Thematic synthesis and meta-analysis were used to synthesize the qualitative and quantitative data extracted from the selected papers. Results: The analysis included 16 studies that met the inclusion criteria and were deemed to be of moderate or higher quality. Among these studies, 4 demonstrated positive results for therapeutic mediation and one for supportive mediation in psychiatric disorders. Additionally, all studies showed positive outcomes for depression and neurological disorders. Regarding stress and anxiety, 3 studies indicated supportive mediation, while 2 studies showed activating mediation. Conclusions: The overall assessment of animal-assisted therapy shows promise as an effective intervention in promoting well-being among diverse populations. Further research and the establishment of standardized outcome assessment measures and comprehensive policies are essential for advancing the field and maximizing the benefits of animal-assisted therapy.

2.
Indian J Ophthalmol ; 72(5): 648-652, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38189451

RESUMO

PURPOSE: To describe the subretinal hyporeflective globule in cases of central serous chorioretinopathy (CSC). METHODS: A retrospective analysis of consecutive cases of CSC presenting to a tertiary eye care center in eastern India was conducted. Subretinal hyporeflective globules were identified as small globular lesions below the external limiting membrane/ellipsoid zone, but above the RPE layer. They had a hyperreflective border with a hyporeflective core and a clear posterior tail of hyper-transmission. RESULTS: The present study analyzed 137 eyes of 137 patients. Eighty (58.4%) eyes had acute disease at presentation, 48 (35%) eyes had chronic disease, and eight (5.8%) eyes had resolved CSC. Subretinal hyporeflective globules were seen in 27 (21.8%) eyes, of which choroidal caverns were seen in seven (5.1%) eyes. Twenty-five eyes with chronic CSC and only two eyes with acute CSC had subretinal hyporeflective globules. Three eyes with resolved CSC had subretinal hyporeflective globules. CONCLUSION: We describe subretinal hyporeflective globule as a novel optical coherence tomography (OCT) finding in cases of CSC and describe its clinical correlates.

3.
ACS Appl Bio Mater ; 7(2): 1158-1168, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38197266

RESUMO

Despite advancements in preventive measures and hospital protocols, surgical site infections (SSIs) remain a significant concern following surgeries. Sutures, commonly used for wound closure, can serve as a platform for microbial adherence and contamination, leading to extensive debridement and recurrent antibiotic therapy. The emergence of drug resistance and the formation of biofilms on sutures have further complicated the management of SSIs. Drug-eluting sutures incorporating biocides like triclosan have limitations due to uncontrolled release and associated toxicity. Therefore, there is a need for alternative approaches to impart antimicrobial properties to sutures. In this study, we present a one-step covalent cross-linking method to coat surgical sutures with an antimicrobial small molecule, quaternary benzophenone-based antimicrobial (QSM). Additionally, the sutures are dip-coated with ibuprofen, a nonsteroidal anti-inflammatory drug with analgesic properties. The coated sutures maintained their morphological and tensile properties after in vivo implantation. The antimicrobial coating demonstrated efficacy against a broad-spectrum pathogens, including drug-resistant bacteria and fungi. The optimized formulation retained its biodegradability in vivo. Furthermore, the coated sutures exhibited ∼3 log reduction in methicillin-resistant Staphylococcus aureus (MRSA) burden in a subcutaneous implantation mouse model. Overall, this multifunctional coating provides antimicrobial properties to surgical sutures while preserving their mechanical integrity and biodegradability. These coated sutures have the potential to address the challenge of SSIs and contribute to improved surgical outcomes.


Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Triclosan , Animais , Camundongos , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/microbiologia , Suturas/efeitos adversos , Triclosan/farmacologia
4.
Sci Rep ; 14(1): 631, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38182678

RESUMO

Probiotics have gained a significant attention as a promising way to improve gut health and overall well-being. The increasing recognition of the potential health advantages associated with functional food products, leading to a specific emphasis on co-encapsulating probiotic bacteria and bioactive compounds within a unified matrix. To further explore this concept, a meta-analysis was performed to assess the effects of probiotics encapsulated in nanoparticles. A comprehensive meta-analysis was conducted, encompassing 10 papers published from 2017 to 2022, focusing on the encapsulation of probiotics within nanoparticles and their viability in various gastrointestinal conditions. The selection of these papers was based on their direct relevance to the research topic. Random-effect models were used to aggregate study-specific risk estimates. In the majority of studies, it was observed that nano-encapsulated nanoparticles showed improved viability over time compared to their free state counterparts. At various time intervals, the odds ratios (OR) with 95% confidence intervals (CI) were estimated using fixed and random effect models. At 0 min, the OR (95%CI) was 2.79 (2.79; 2.80) and 2.38 (2.14; 2.64) for. At 30 and 60 min observation was at similar rate of 2.23 (2.23; 2.24) and 2.05 (1.73; 2.43). However, at 90 min it was 1.39 (1.39; 1.39) and 1.66 (1.29; 2.14) and at 120 min 2.41 (2.41; 2.42) and 2.03 (1.63; 2.52). Overall evaluation of encapsulation revealed an improvement in probiotic bacterial viability in simulated the gastrointestinal environments.


Assuntos
Nanopartículas , Probióticos , Alimento Funcional , Viabilidade Microbiana , Razão de Chances
5.
Chem Sci ; 15(1): 259-270, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38143555

RESUMO

Gram-negative bacterial infections pose a significant challenge due to two major resistance elements, including the impermeability of the outer membrane and the overexpression of efflux pumps, which contribute to antibiotic resistance. Additionally, the coexistence of multispecies superbugs in mixed species biofilms further complicates treatment, as these infections are refractory to most antibiotics. To address this issue, combining obsolete antibiotics with non-antibiotic adjuvants that target bacterial membranes has shown promise in combating antibacterial resistance. However, the clinical translation of this cocktail therapy has been hindered by the toxicity associated with these membrane active adjuvants, mainly due to a limited understanding of their structure and mechanism of action. Towards this goal, herein, we have designed a small molecular adjuvant by tuning different structural parameters, such as the balance between hydrophilic and hydrophobic groups, spatial positioning of hydrophobicity and hydrogen bonding interactions, causing moderate membrane perturbation in bacterial cells without any toxicity to mammalian cells. Moderate membrane perturbation not only enhances the internalization of antibiotics, but also increases the intracellular concentration of drugs by hampering the efflux machinery. This revitalises the efficacy of various classes of antibiotics by 32-512 fold, without inducing toxicity. The leading combination not only exhibits potent bactericidal activity against A. baumannii biofilms but also effectively disrupts mature multispecies biofilms composed of A. baumannii and methicillin-resistant Staphylococcus aureus (MRSA), which is typically resistant to most antibiotics. Importantly, the combination therapy demonstrates good biocompatibility and excellent in vivo antibacterial efficacy (>99% reduction) in a skin infection model of A. baumannii. Interestingly, A. baumannii shows reduced susceptibility to develop resistance against the leading combination, underscoring its potential for treating multi-drug resistant infections.

6.
BMC Microbiol ; 23(1): 291, 2023 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-37845637

RESUMO

BACKGROUND: Antimicrobial resistance (AMR) is a critical global issue that poses significant threats to human health, animal welfare, and the environment. With the increasing emergence of resistant microorganisms, the effectiveness of current antimicrobial medicines against common infections is diminishing. This study aims to conduct a competitive meta-analysis of surveillance data on resistant microorganisms and their antimicrobial resistance patterns in two countries, Egypt and the United Kingdom (UK). METHODS: Data for this study were obtained from published reports spanning the period from 2013 to 2022. In Egypt and the UK, a total of 9,751 and 10,602 food samples were analyzed, respectively. Among these samples, 3,205 (32.87%) in Egypt and 4,447 (41.94%) in the UK were found to contain AMR bacteria. RESULTS: In Egypt, the predominant resistance was observed against ß-lactam and aminoglycosides, while in the United Kingdom, most isolates exhibited resistance to tetracycline and ß-lactam. The findings from the analysis underscore the increasing prevalence of AMR in certain microorganisms, raising concerns about the development of multidrug resistance. CONCLUSION: This meta-analysis sheds light on the escalating AMR problem associated with certain microorganisms that pose a higher risk of multidrug resistance development. The significance of implementing One Health AMR surveillance is emphasized to bridge knowledge gaps and facilitate accurate AMR risk assessments, ensuring consumer safety. Urgent actions are needed on a global scale to combat AMR and preserve the effectiveness of antimicrobial treatments for the well-being of all living beings.


Assuntos
Anti-Infecciosos , Saúde Única , Animais , Humanos , Antibacterianos/uso terapêutico , beta-Lactamas , Farmacorresistência Bacteriana , Egito , Reino Unido
7.
Biomolecules ; 13(8)2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37627247

RESUMO

Antimicrobial resistance (AMR) is a growing public health concern worldwide, and it poses a significant threat to human, animal, and environmental health. The overuse and misuse of antibiotics have contributed significantly and others factors including gene mutation, bacteria living in biofilms, and enzymatic degradation/hydrolyses help in the emergence and spread of AMR, which may lead to significant economic consequences such as reduced productivity and increased health care costs. Nanotechnology offers a promising platform for addressing this challenge. Nanoparticles have unique properties that make them highly effective in combating bacterial infections by inhibiting the growth and survival of multi-drug-resistant bacteria in three areas of health: human, animal, and environmental. To conduct an economic evaluation of surveillance in this context, it is crucial to obtain an understanding of the connections to be addressed by several nations by implementing national action policies based on the One Health strategy. This review provides an overview of the progress made thus far and presents potential future directions to optimize the impact of nanobiotics on AMR.


Assuntos
Antibacterianos , Saúde Única , Animais , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Biofilmes , Análise Custo-Benefício
8.
ACS Biomater Sci Eng ; 9(7): 4404-4414, 2023 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-37335583

RESUMO

Microbial colonization on urinary and intravascular catheter surfaces results in steeply rising cases of catheter-associated infections as well as blood stream infections. Currently marketed efforts include impregnation and loading of antimicrobials and antiseptics that leach out into the local environment and inactivate microbes. However, they suffer from uncontrolled release, induction of resistance, and undesired toxicity. Here, in this manuscript, we have developed a photocurable, covalent coating on catheters using quaternary benzophenone-based amide (QSM-1). The coating was found to be active against drug-resistant bacteria and fungi. The coating inactivated stationary and persister cells of superbug MRSA and inhibited the formation of biofilms with retained activity against broad-spectrum bacteria when challenged in realistic urinary conditions. The coating was seen to be biocompatible in vitro and in vivo. Remarkably, the coated catheters showed reduced fouling and >99.9% reduction in bacterial burden when implanted in vivo in a mice model of subcutaneous implantation. We conceive the possibility of application of QSM-1-coated catheters in the healthcare settings to tackle the notorious catheter-associated nosocomial infections.


Assuntos
Anti-Infecciosos , Infecções Relacionadas a Cateter , Camundongos , Animais , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/prevenção & controle , Infecções Relacionadas a Cateter/microbiologia , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Catéteres , Biofilmes
9.
Pharmaceutics ; 15(2)2023 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-36839932

RESUMO

Many novel medical therapies use nanoparticle-based drug delivery systems, including nanomaterials through drug delivery systems, diagnostics, or physiologically active medicinal products. The approval of nanoparticles with advanced therapeutic and diagnostic potentials for applications in medication and immunization depends strongly on their synthesizing procedure, efficiency of functionalization, and biological safety and biocompatibility. Nanoparticle biodistribution, absorption, bioavailability, passage across biological barriers, and biodistribution are frequently assessed using bespoke and biological models. These methods largely rely on in vitro cell-based evaluations that cannot predict the complexity involved in preclinical and clinical studies. Therefore, assessing the nanoparticle risk has to involve pharmacokinetics, organ toxicity, and drug interactions manifested at multiple cellular levels. At the same time, there is a need for novel approaches to examine nanoparticle safety risks due to increased constraints on animal exploitation and the demand for high-throughput testing. We focus here on biological evaluation methodologies that provide access to nanoparticle interactions with the organism (positive or negative via toxicity). This work aimed to provide a perception regarding the risks associated with the utilization of nanoparticle-based formulations with a particular focus on assays applied to assess the cytotoxicity of nanomaterials.

10.
Biomater Sci ; 11(3): 998-1012, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36541679

RESUMO

The continuous intervention of multidrug-resistant (MDR) bacterial infections worsens and slows the dynamicity of natural wound healing processes. Fortunately, antibiotics, metal ions, or metal nanoparticle-loaded antimicrobial hydrogels have been developed to tackle infections at injury sites and speed up the healing process. Despite their success, these marketed released based hydrogels are still limited owing to their lack of broad-spectrum activity, inability to tackle biofilm-associated infections, susceptibility towards resistance development, fast release kinetics, and mild to moderate toxicity. To address these shortcomings, we report the development of a biocompatible, shear-thinning, injectable gellan-gelatin hydrogel loaded with a peptidomimetic potent biocide (ASAM-10). The hydrogel upon sustained biocide release (60% within 72 h), displays a broad-spectrum antibacterial activity with negligible in vitro (hemolysis < 20%) and in vivo toxicity (no adverse effects on dermal layer of mice). Besides tackling bacterial dormant subpopulation (1-6 Log reduction), the optimized hydrogel is able to disrupt the preformed bacterial biofilm and even kill the biofilm-trapped pathogens with enhanced pathogenicity. Above all, the lead hydrogel was proficient in tackling methicillin-resistant Staphylococcus aureus (MRSA) wound infections in a mouse model through its safe topical administration. Overall, the biocide-loaded hydrogel can be considered as a promising candidate to combat MDR chronic infections at the wound site.


Assuntos
Anti-Infecciosos , Desinfetantes , Staphylococcus aureus Resistente à Meticilina , Camundongos , Animais , Hidrogéis , Antibacterianos/farmacologia
11.
Antibiotics (Basel) ; 13(1)2023 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-38247576

RESUMO

The "One Health" initiative is a critical strategy that recognizes the interconnectedness between human, animal, and environmental health in the spread and containment of infectious pathogens. With the ease of global transportation, transboundary disease outbreaks pose a significant threat to food safety and security, endangering public health and having a negative economic impact. Traditional diagnostic techniques based on genotypic and phenotypic analyses are expensive, time-consuming, and cannot be translated into point-of-care tools, hindering effective disease management and control. However, with advancements in molecular methods, biosensors, and new generation sequencing, rapid and reliable diagnostics are now available. This review provides a comprehensive insight into emergent viral and bacterial pathogens and antimicrobial resistance, highlighting the importance of "One Health" in connecting detection and effective treatment. By emphasizing the symbiotic relationship between human and animal health, this paper underscores the critical role of "One Health" initiatives in preventing and controlling infectious diseases.

13.
ACS Appl Mater Interfaces ; 14(37): 42483-42493, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36073910

RESUMO

Microbial adhesion and contamination on shared surfaces can lead to life-threatening infections with serious impacts on public health, economy, and clinical practices. The traditional use of chemical disinfectants for sanitization of surfaces, however, comes with its share of health risks, such as hazardous effects on the eyes, skin, and respiratory tract, carcinogenicity, as well as environmental toxicity. To address this, we have developed a nonleaching quaternary small molecule (QSM)-based sprayable coating which can be fabricated on a wide range of surfaces such as nylon, polyethylene, surgical mask, paper, acrylate, and rubber in a one-step, photocuring technique. This contact-active coating killed pathogenic bacteria and fungi including drug-resistant strains of Staphylococcus aureus and Candida albicans within 15-30 min of contact. QSM coatings withstood multiple washes, highlighting their durability. Interestingly, the coated surfaces exhibited rapid killing of pathogens, leading to the prevention of their transmission upon contact. The coating showed membrane disruption of bacterial cells in fluorescence and electron microscopic investigations. Along with bacteria and fungi, QSM-coated surfaces also showed the complete killing of high loads of influenza (H1N1) and SARS-CoV-2 viruses within 30 min of exposure. To our knowledge, this is the first report of a coating for multipurpose materials applied in high-touch public places, hospital equipment, and clinical consumables, rapidly killing drug-resistant bacteria, fungi, influenza virus, and SARS-CoV-2.


Assuntos
Anti-Infecciosos , COVID-19 , Desinfetantes , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Acrilatos/farmacologia , Antibacterianos/química , Anti-Infecciosos/farmacologia , Bactérias , COVID-19/prevenção & controle , Desinfetantes/farmacologia , Fungos , Humanos , Nylons/farmacologia , Polietilenos/farmacologia , Borracha , SARS-CoV-2
14.
ACS Appl Bio Mater ; 5(8): 3951-3959, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35912488

RESUMO

Surges in infectious diseases and their transmission in households and commercial and healthcare settings have increased the use of polymeric materials as protective covers. Despite ongoing efforts, conventional polymeric materials still pose the threat of surface-associated transmission of pathogens due to the fact that they lack antimicrobial properties. Here, we have developed an easy-to-fabricate polymeric sheet [quaternary polymeric transparent sheet (QPTS)] that shows an excellent antimicrobial property and is also transparent in nature, increasing its practical applications in a wide range of surfaces. The sheet was fabricated by combining cationic amphiphilic water-soluble polyethylenimine derivative (QPEINH-C6) and poly(vinyl alcohol) (PVA). The optimum composition (QPTS-3) exhibited a complete reduction of bacterial and fungal infection (∼3-4 log reduction) within 15 min. QPTS-3 also exhibited activity against antibiotic-insusceptible metabolically inactive bacterial cells. The sheet prevented the growth of MRSA biofilm even after 72 h of incubation, which was confirmed through electron microscopy on the QPTS sheet. Most importantly, ∼99.9% of the influenza viral load was reduced completely within 30 min of exposure of the sheet. Apart from the antimicrobial property, the sheet successfully retained its transparency (∼88%) and maintained a significant mechanical strength (∼15 N), highlighting its potential applications in commercial and healthcare settings.


Assuntos
Anti-Infecciosos , Álcool de Polivinil , Antibacterianos , Anti-Infecciosos/farmacologia , Biofilmes , Polímeros
15.
ACS Biomater Sci Eng ; 8(8): 3596-3607, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35802178

RESUMO

Hemorrhage during accidents or surgery is a significant challenge that can contribute to mortality. This is further aggravated due to bacterial infections at the injured site. Therefore, rapid application of a hemostatic and antibacterial material is highly necessary as a pretreatment for patients' survival. Herein, we have developed a hemostatic sponge (Hemobac) through amide crosslinking of gelatin and an N-(2-hydroxy) propyl-3-trimethylammonium chitosan (HTCC)-silver chloride nanocomposite (QAm1-Ag0.1) to mitigate bacterial infections, while aiding hemostasis. This Hemobac sponge completely eradicated (∼4-5 log) a wide range of Gram-positive and Gram-negative bacteria encompassing various clinical isolates within 6 h. The antihemorrhagic ability of Hemobac was ascertained through SEM images, which exhibited the presence of agglomerated blood cells onto the sponge with a significantly low blood-clotting index value (∼23 ± 1). Notably, Hemobac reduced the blood loss by ∼70-80% in the liver puncture model and femoral vein injury model in mice, displaying its improved hemostatic ability over a marketed gelatin-based sponge. Negligible hemolytic activity (∼6%) and retained healthy morphology of mammalian cells were observed upon exposure to the Hemobac sponge. Minimal immune response was noticed at the Hemobac-treated wound in mice through histopathology analysis. Collectively, these findings indicate that this biocompatible Hemobac sponge can stop the bleeding instantaneously and combat bacterial infections.


Assuntos
Hemostáticos , Animais , Antibacterianos/farmacologia , Gelatina/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Hemorragia , Hemostasia , Hemostáticos/farmacologia , Mamíferos , Camundongos
16.
ACS Appl Mater Interfaces ; 14(30): 34527-34537, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35875986

RESUMO

The increasing incidence of microbial infections and a limited arsenal of effective antibacterial and antifungal agents have entailed the need for new broad-spectrum therapeutics. Polymer-inorganic nanocomposites have emerged as an integral choice of antimicrobials but are limited by complicated synthesis, narrow-spectrum activity, and poor in vivo efficacy. Herein, chloride counterions of a nontoxic, moderately antibacterial polymer have been explored for in situ nanoprecipitation-based synthesis of water-soluble polymer-silver chloride nanocomposites. With the controlled release of silver ions, the nanocomposites were highly active against multidrug-resistant bacteria as well as fluconazole-resistant fungi. Alongside the elimination of metabolically inactive bacterial cells, the nanocomposites disrupted polymicrobial biofilms, unlike antibiotics and only silver-based ointments. This underlined the role of the engineered composite design, where the polymer interacted with the biofilm matrix, facilitating the penetration of nanoparticles to kill microbes. Further, the nanocomposite diminished Pseudomonas aeruginosa burden in mice skin infection (>99.9%) with no dermal toxicity proving its potential for clinical translation.


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Nanocompostos , Animais , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Biofilmes , Nanopartículas Metálicas/uso terapêutico , Camundongos , Testes de Sensibilidade Microbiana , Nanocompostos/uso terapêutico , Nanocompostos/toxicidade , Polímeros/farmacologia , Prata/farmacologia
17.
Adv Healthc Mater ; 11(15): e2200536, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35665490

RESUMO

With the increasing focus on healthcare research in the current times, therapeutic and biomaterial interventions for healing of wounds and mitigation of wound-associated infections have seen expedited progress. Conventional approaches consist of release-active gels, which demonstrate leaching of antimicrobials, such as antibiotics, metal ions, etc. However, these systems suffer from the disadvantages of burst release, reservoir exhaustion, and associated toxicity. In this report, intrinsically antimicrobial hydrogel (HyDex) is developed by one-pot UV crosslinking of methacrylated dextran, polyethylene glycol diacrylate, and cationic lipophilic methacrylate with varied hydrophobic chain, which displays broad-spectrum antimicrobial activity, hemostatic ability, and rapid wound closure efficacy. The optimized hydrogel exhibits potent antimicrobial efficacy against multidrug-resistant Gram-positive and Gram-negative bacteria as well as against pathogenic fungus Candida albicans. The HyDex hydrogel shows rapid arrest of bleeding in mice liver puncture model. The hydrogel kills carbapenem-resistant Acinetobacter baumannii in a murine model of burn wound infection with >99% reduction in bacterial burden. Furthermore, this hydrogel displays significant reduction in inflammatory responses, with accelerated wound healing in rat deep wound model. Collectively, these results imply the excellent promise held by lead hydrogel to be developed for tackling deep tissue wounds, notorious infections, and resulting inflammatory responses.


Assuntos
Anti-Infecciosos , Infecção dos Ferimentos , Animais , Antibacterianos/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Hidrogéis/química , Camundongos , Ratos , Cicatrização , Infecção dos Ferimentos/tratamento farmacológico
18.
Antibiotics (Basel) ; 11(4)2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35453227

RESUMO

Biofilm production by bacteria is presumed to be a survival strategy in natural environments. The production of biofilms is known to be influenced by a number of factors. This paper has precisely elaborated on the different factors that directly influence the formation of biofilm. Biofilm has serious consequences for human health, and a variety of infections linked to biofilm have emerged, rapidly increasing the statistics of antimicrobial resistance, which is a global threat. Additionally, to combat resistance in biofilm, various approaches have been developed. Surface modifications, physical removal, and the use of nanoparticles are the recent advances that have enabled drug discovery for treating various biofilm-associated infections. Progress in nanoparticle production has led to the development of a variety of biofilm-fighting strategies. We focus on the present and future therapeutic options that target the critical structural and functional characteristics of microbial biofilms, as well as drug tolerance mechanisms, such as the extracellular matrix, in this review.

19.
ACS Infect Dis ; 8(5): 1086-1097, 2022 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-35404568

RESUMO

Combination therapy with membrane-targeting compounds is at the forefront because the bacterial membrane is an attractive target considering its role in various multidrug-resistant elements. However, this strategy is crippled by the toxicity associated with these agents. The structural requirements for optimum membrane perturbation and minimum toxicity have not been explored for membrane-targeting antibiotic potentiators or adjuvants. Here, we report the structural influence of different chemical moieties on membrane perturbation, activity, toxicity, and potentiating ability in norspermidine derivatives. It has been shown in this report that weak membrane perturbation, achieved by the incorporation of cyclic hydrophobic moieties, is an effective strategy to design antibiotic adjuvants with negligible in vitro toxicity and activity but good potentiating ability. Aryl or adamantane functionalized derivatives were found to be better resorts as opposed to the acyclic analogues, exhibiting as high as 4096-fold potentiation of multiple classes of antibiotics toward critical Gram-negative superbugs. The mechanism of potentiation was nonspecific, consisting of weak outer-membrane permeabilization, membrane depolarization, and efflux inhibition. This unique concept of "weakly perturbing the membrane" by incorporating cyclic hydrophobic moieties in a chemical design with free amine groups serves as a breakthrough for nontoxic membrane-perturbing adjuvants and has the potential to revitalize the effect of obsolete antibiotics to treat complicated Gram-negative bacterial infections.


Assuntos
Antibacterianos , Infecções por Bactérias Gram-Negativas , Adjuvantes Farmacêuticos/farmacologia , Antibacterianos/química , Bactérias Gram-Negativas , Humanos
20.
Biomater Sci ; 10(8): 2014-2028, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35294508

RESUMO

Various drug resistant pathogens such as bacteria, fungi and viruses enter a host through different routes, which can lead to health-related problems and even fatalities. Propagation of these infectious microbes majorly occurs through the mucosal openings or upon topical contact. To curb their transmission or to cure infections associated with these pathogens, herein we describe the development of an antimicrobial hydrogel, based on a water soluble quaternary lipophilic polyethyleneimine derivative (QPEINH-C6). The cationic polymer QPEINH-C6 exhibited antibacterial activity against drug-resistant Gram-positive bacteria (MIC = 10-62 µg mL-1) and Gram-negative bacteria (MIC = 117-123 µg mL-1). The derivative showed killing of human pathogenic fungi (MIC = 58-67 µg mL-1), including their clinical isolates. The rapid bactericidal and fungicidal nature were confirmed from the fast inactivation kinetics of bacterial cells (methicillin resistant S. aureus and vancomycin resistant S. aureus) within 3-6 hours and C. albicans within 1 h with ∼5-6 log reduction in the microbial burden. This antibacterial and antifungal cationic polymer was then used to construct an antimicrobial shear-thinning hydrogel (Bacfuvir), through non-covalent crosslinking with biocompatible gellan and polyvinyl alcohol (PVA). This hydrogel displayed ∼5-7 log reduction of numerous multidrug-resistant bacteria and their stationary phase cells which are insusceptible to conventional antibiotics. In addition, >99.9 % viable bacterial burden was reduced from preformed biofilm matrices of drug-resistant bacteria. Alongside, fluconazole-resistant C. albicans strains were killed completely within 15-60 min upon exposure to Bacfuvir gel. Most importantly, MRSA and C. albicans cells were reduced (3-4 log) in polymicrobial biofilms after hydrogel treatment. The hydrogel exhibited 99.9 % reduction of influenza viruses in a rapid manner. Due to the biocompatibility of Bacfuvir gel on topical application in a murine model and easy administration owing to its shear-thinning behaviour, this hydrogel can markedly contribute to mitigating drug-resistant bacterial, fungal and viral infections in healthcare settings.


Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Orthomyxoviridae , Animais , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Bactérias , Biofilmes , Fungos , Humanos , Hidrogéis/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Polímeros/farmacologia
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