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1.
Int J Nanomedicine ; 15: 6935-6944, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061360

RESUMO

Introduction: Nanoparticle solutions have been studied to improve antimicrobial effect. The aim of this study was to develop, characterize, and evaluate the in vitro and in vivo antiseptic efficacy of 0.25% aqueous-based chlorhexidine nanoemulsion (NM-Cl 0.25% w/v). Methods: The NM-Cl 0.25% w/v (2.5mg/mL) and free chlorhexidine nanoemulsion (FCN; same composition of NM-Cl without the molecule of chlorhexidine) were synthetized by the spontaneous emulsification method. Characterization analyses of physical and chemical properties were performed. The NM-Cl 0.25% w/v was compared with chlorhexidine 0.5% alcohol base (CS-Cl 0.5%) in vitro studies (microdilution study and kill curve study), and in vivo study (antisepsis of rats dorsum). Kruskal-Wallis test was used between groups and inside the same group, at different sample times and the Mann-Whitney test was performed when difference was detected. Results: The NM-Cl 0.25% w/v presented adequate physicochemical characteristics for a nanoemulsion, revealing a more basic pH than FCN and difference between zeta potential of NM-Cl 0.25% w/v and FCN. The NM-Cl 0.25% w/v and CS-Cl 0.5% solutions were more effective on Gram-positive than on Gram-negative bacteria (p≤0.05). NM-Cl 0.25% w/v presented upper antiseptic effect in the microdilution study and residual antiseptic effect was maintained for a longer time when compared to CS-Cl 0.5% (kill curve study). The four-fold (minimal inhibitory concentration) of NM-Cl 0.25% were the formulations with most durable effect within those tested, presenting residual effect until T6 for both bacteria. In the in vivo study, both formulations (NM-Cl 0.25% w/v and CS-Cl 0.5%) had a reduction of the microorganisms in the skin of the rats (p<0.0001) not revealing any difference between the formulations at different times, showing the antiseptic effect of NM-Cl (p≤0.05). Conclusion: Both in vitro and in vivo experiments demonstrated that NM-Cl showed promising future as an antiseptic for cutaneous microbiota.


Assuntos
Anti-Infecciosos Locais/farmacologia , Clorexidina/farmacologia , Emulsões/química , Nanoestruturas/química , Animais , Anti-Infecciosos Locais/química , Clorexidina/química , Emulsões/farmacologia , Etanol/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Masculino , Testes de Sensibilidade Microbiana , Nanoestruturas/uso terapêutico , Ratos Wistar , Pele/efeitos dos fármacos , Pele/microbiologia
2.
J Cosmet Dermatol ; 19(2): 270-277, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31904191

RESUMO

BACKGROUND: Hypochlorous acid (HOCl), a naturally occurring molecule produced by the immune system, is highly active against bacterial, viral, and fungal microorganisms. Moreover, HOCl is active against biofilm and increases oxygenation of the wound site to improve healing. Natural HOCl is unstable; through technology, it can be stabilized into an effective topical antiseptic agent. AIM: This paper focuses on the use of topical stabilized HOCl in wound and scar management for pre-, peri-, and postprocedures-including its ability to reduce the occurrence hypertrophic scars and keloids. The role of the product in other skin conditions is beyond the scope of this article. METHODS: A panel comprising clinicians with experience in cosmetic and surgical procedures met late 2018 to discuss literature search results and their own current clinical experience regarding topical stabilized HOCl. The panel of key opinion leaders in dermatology and plastic surgery defined key insights and consensus statements on the direction of use for the product. RESULTS: Topical stabilized HOCl provides an optimal wound healing environment and, when combined with silicone, may be ideal for reducing scarring. Additionally, in contrast to chlorhexidine, HOCl, used as an antiseptic skin preparation, raises no concerns of ocular- or ototoxicity. CONCLUSIONS: For wound care and scar management, topical stabilized HOCl conveys powerful microbicidal and antibiofilm properties, in addition to potency as a topical wound healing agent. It may offer physicians an alternative to other less desirable wound care measures.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Cicatriz Hipertrófica/prevenção & controle , Ácido Hipocloroso/administração & dosagem , Queloide/prevenção & controle , Procedimentos Cirúrgicos Reconstrutivos/efeitos adversos , Infecção da Ferida Cirúrgica/tratamento farmacológico , Administração Cutânea , Anti-Infecciosos Locais/efeitos adversos , Anti-Infecciosos Locais/química , Biofilmes/efeitos dos fármacos , Cicatriz Hipertrófica/etiologia , Humanos , Ácido Hipocloroso/efeitos adversos , Ácido Hipocloroso/química , Queloide/etiologia , Assistência Perioperatória/normas , Período Perioperatório , Padrão de Cuidado , Infecção da Ferida Cirúrgica/etiologia , Cicatrização/efeitos dos fármacos
3.
AAPS PharmSciTech ; 21(2): 43, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31897806

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) is considered a common colonizer of burn wound and accounts for high morbidity and mortality all across the globe. Systemic antibiotic therapy which is generally prescribed for these patients has a number of limitations. These include high drug dose, toxicity, and chances of development of drug resistance. However, local delivery of drug not only addresses these limitations but also provides better efficacy at the site of infection. In the present study, hydrogel preparations were developed for the topical delivery of moxifloxacin for the treatment of S. aureus-infected burn wound. Moxifloxacin was characterized by UV, FTIR, DSC, hot-stage microscopy, NMR, and HPLC and loaded into conventional and Boswellia-containing novel gels. Gels were characterized by visual examination, pH, UV spectroscopy, and release assays. In vivo studies showed that both gels were effective in eradicating the bacteria completely from the wound site when treatment was started during the early stage of infection. On the contrary, delayed treatment of planktonic and biofilm cells with novel gel showed better efficacy as compared with conventional gel in S. aureus-infected burn wound. Histopathological analysis also showed better skin healing efficacy of novel gel than conventional gel. Our results show that moxifloxacin can be efficiently used topically in the management of burn wound infections along with other antibacterial agents. Since biofilm-mediated infections are on the rise especially in chronic bacterial disease, therefore, a preparation containing antibiofilm agent-like Boswellia as one of the excipients would be more meaningful.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/farmacologia , Biofilmes/efeitos dos fármacos , Queimaduras/complicações , Quitosana/química , Hidrogéis/química , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Animais , Antibacterianos/química , Anti-Infecciosos Locais/química , Boswellia/química , Composição de Medicamentos , Géis , Staphylococcus aureus Resistente à Meticilina , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Moxifloxacina/administração & dosagem , Moxifloxacina/química , Moxifloxacina/uso terapêutico , Infecções Estafilocócicas/microbiologia , Infecção dos Ferimentos/microbiologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-31762378

RESUMO

Triclosan (TCS) is widely used in personal care products and acts as an antibacterial agent. Residues of TCS may have potential effects on the human health. In this article, the interaction between TCS and bovine serum albumin (BSA) has been characterized by using multi-spectroscopic approaches and molecular docking method under physiological conditions. Thermodynamic investigations revealed that TCS spontaneously bound to a binding site of BSA and hydrogen bonds played a dominant role in this process. The site marker competition experiments indicated that TCS bound at site II (subdomain IIIA) of BSA, which was well substantiated by molecular docking. The binding of TCS further led to changes of conformation and microenvironment of BSA. This work explored the interaction of TCS with BSA, which might be beneficial for evaluating the binding mechanism of other environmental pollutant at molecular level.


Assuntos
Anti-Infecciosos Locais/química , Soroalbumina Bovina/química , Triclosan/química , Sítios de Ligação , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Conformação Proteica , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Termodinâmica
5.
Biochem Pharmacol ; 171: 113713, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31733192

RESUMO

Oral cancer is a prevalent cancer in male worldwide. Oral potentially malignant disorders (OMPDs) are the oral mucosa lesions that have high malignant transformation rate to oral cancer. The mainstay for OMPDs treatment includes carbon dioxide (CO2) laser and surgery, which may lead to the side effects of scarring and impaired function of oral cavity in the patients and reduced their willingness to receive curative therapy. Therefore, developing a non-invasive and function-preserving therapy is clinically important. Since development of a novel chemotherapeutic drug requires a lot of time and cost, we applied the high-throughput screening (HTS) approach to identify new bioactivities for FDA-approved drugs, known as drug repurposing. Through this drug repurposing approach, we discovered that gentian violet (GV), which is well known for its antibacterial, antifungal, antihelminthic, antitrypanosomal and antiviral activities, was able to induce significant cell death in DOK oral precancerous cells through ROS production. Moreover, decreased phosphorylation of p53(Ser15) and NFκB(Ser536) was required for GV-induced cell death. In vivo, 3% GV orabase effectively suppressed the progression of DMBA-induced oral precancerous lesions. In conclusion, this new formulation of GV through drug repurposing has the potential to be further developed as a therapeutic drug for OPMD clinically.


Assuntos
Carboximetilcelulose Sódica/análogos & derivados , Reposicionamento de Medicamentos/métodos , Violeta Genciana/farmacologia , Mucosa Bucal/efeitos dos fármacos , Neoplasias Bucais/metabolismo , Animais , Anti-Infecciosos Locais/química , Anti-Infecciosos Locais/farmacologia , Carboximetilcelulose Sódica/química , Linhagem Celular , Linhagem Celular Tumoral , Cricetinae , Violeta Genciana/química , Ensaios de Triagem em Larga Escala/métodos , Humanos , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Lesões Pré-Cancerosas/tratamento farmacológico , Lesões Pré-Cancerosas/patologia , Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
6.
J Environ Sci Health B ; 55(1): 52-59, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31453744

RESUMO

Multi-spectroscopic and molecular docking methods were used to study the interaction between triclosan (TCS) and bovine serum albumin (BSA). The results indicated that the fluorescence quenching of BSA by TCS was due to the formation of TCS-BSA complex through static quenching. This result was also demonstrated by time-resolved fluorescence experiment. The binding constants and number of binding sites between TCS and BSA were 1.30 × 105 M-1 and 1.17 at 298 K, respectively. The thermodynamic parameters were studied in detail which suggested that hydrophobic forces and hydrogen bond played major roles in the TCS-BSA interaction. Moreover, the site marker competitive experiments and docking studies revealed that TCS could bind BSA into site I in subdomain IIA. All the results of UV-vis spectrophotometry, circular dichroism spectroscopy and synchronous fluorescence spectroscopy showed that interaction between TCS and BSA induced conformation changes of BSA.


Assuntos
Soroalbumina Bovina/química , Triclosan/química , Animais , Anti-Infecciosos Locais/química , Sítios de Ligação , Bovinos , Dicroísmo Circular , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Conformação Proteica , Soroalbumina Bovina/metabolismo , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Termodinâmica , Triclosan/metabolismo
7.
Biomed Pharmacother ; 130: 110624, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33503761

RESUMO

Australian tea tree (Melaleuca alternifolia) oil (TTO) and its monoterpene constituents such as terpinen-4-ol (T4O), 1,8-cineole, limonene, p-cymene, and α-terpinene have been shown to be effective in controlling a wide range of parasitic infections. The anti-parasitic effects of these compounds are mainly due to their anti-histamine and anti-acetylcholinesterase activities as well as their ability to modulate host inflammatory responses. This review attempts to summarize recent advances in the uses of TTO and its 15 major monoterpene constituents in treating parasitic infections in both humans and animals. Activities against parasitic protozoans (Plasmodium falciparum, Leishmania spp., Trypanosoma spp., Acanthamoeba castellanii, Trichomonas vaginalis, Eimeria, and Ichthyophthirius multifiliis), nematodes (Haemonchus contortus and Anisakis simplex), cestode (Echinococcus ortleppi), and monogeneans (Gasterosteus spp. and Dactylogyrus minutus) have been reported, showing good potentials in treating parasitic infections. Further studies are necessary for developing anti-parasite therapies using TTO or its monoterpenes constituents.


Assuntos
Anti-Infecciosos Locais/farmacologia , Anti-Infecciosos Locais/uso terapêutico , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Helmintíase/tratamento farmacológico , Monoterpenos/farmacologia , Monoterpenos/uso terapêutico , Infecções por Protozoários/tratamento farmacológico , Óleo de Melaleuca/farmacologia , Óleo de Melaleuca/uso terapêutico , Animais , Anti-Infecciosos Locais/química , Helmintíase/parasitologia , Humanos , Melaleuca/química , Monoterpenos/química , Infecções por Protozoários/parasitologia , Óleo de Melaleuca/química
8.
Int J Pharm ; 572: 118833, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31715363

RESUMO

Different types of in-situ forming implants based on poly(lactic-co-glycolic acid) (PLGA) for the controlled dual release of an antiseptic drug (chlorhexidine) and an anti-inflammatory drug (ibuprofen) were prepared and thoroughly characterized in vitro. N-methyl-pyrrolidone (NMP) was used as water-miscible solvent, acetyltributyl citrate (ATBC) as plasticizer and hydroxypropyl methylcellulose (HPMC) was added to enhance the implants' stickiness/bioadhesion upon formation within the periodontal pocket. Different drug forms exhibiting substantially different solubilities were used: chlorhexidine dihydrochloride and digluconate as well as ibuprofen free acid and lysinate. The initial drug loadings were varied from 1.5 to 16.1%. In vitro drug release, dynamic changes in the pH of the surrounding bulk fluid and in the systems' wet mass as well as polymer degradation were monitored. Importantly, the release of both drugs, chlorhexidine and ibuprofen, could effectively be controlled simultaneously during several weeks. Interestingly, the tremendous differences in the drug forms' solubilities (e.g., factor >5000) did not translate into major differences in the resulting release kinetics. In the case of ibuprofen, this can likely (at least in part) be attributed to significant drug-polymer interactions (ibuprofen acts as a plasticizer for PLGA). In the case of chlorhexidine, the release of the much less soluble dihydrochloride was even faster compared to the more soluble digluconate (when combined with ibuprofen free acid). In the case of ibuprofen, at higher initial drug loadings also limited solubility effects within the implants seem to play a role, in contrast to chlorhexidine. In the latter case, instead, increased system porosity effects likely dominate at higher drug loadings.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Clorexidina/administração & dosagem , Ibuprofeno/administração & dosagem , Adesividade , Anti-Infecciosos Locais/química , Anti-Inflamatórios não Esteroides/química , Química Farmacêutica , Clorexidina/química , Preparações de Ação Retardada , Combinação de Medicamentos , Implantes de Medicamento , Liberação Controlada de Fármacos , Excipientes/química , Ibuprofeno/química , Doenças Periodontais/tratamento farmacológico , Plastificantes/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Porosidade , Solubilidade , Solventes/química
9.
Dermatitis ; 30(6): 336-341, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31724988

RESUMO

Health care workers may be at risk of occupational allergic contact dermatitis because of their frequent exposure to medical hand skin cleansers. We identified American Contact Dermatitis Society Core 80 Allergens found in medical hand skin cleansers (waterless skin soaps, water-needed skin soaps, and skin disinfectants) in the United States and developed a list of "low-allergen" medical hand skin cleansers. Waterless skin soaps most commonly contained fragrance, tocopherol, and sodium benzoate. Top allergens in water-needed skin soaps included fragrance, chloroxylenol, propylene glycol, and cocamidopropyl betaine. The most common allergens identified in skin disinfectants were chlorhexidine, cocamide diethanolamine, and fragrance. We identified 11 waterless skin soaps that were free of American Contact Dermatitis Society Core 80 Allergens. Low-allergen products were also identified for water-needed skin soaps (2 products) and skin disinfectants (4 products). This information is accurate as of the date of publication; product availability and ingredients may change over time.


Assuntos
Alérgenos/efeitos adversos , Anti-Infecciosos Locais/química , Dermatite Alérgica de Contato/etiologia , Dermatite Ocupacional/etiologia , Dermatoses da Mão/induzido quimicamente , Higienizadores de Mão/química , Sabões/química , Infecção Hospitalar/prevenção & controle , Pessoal de Saúde , Humanos
10.
Dermatitis ; 30(6): 363-370, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31724990

RESUMO

BACKGROUND: Both surgical personnel and patients undergoing procedures are exposed regularly to different antiseptic chemicals in various forms. Little is known about the ingredients in these antiseptics and the risk these products may provoke allergic contact dermatitis. OBJECTIVE: The aim of the study was to identify and characterize common allergens in surgical scrubs and patient surgical cleansers that health care workers and surgical patients may encounter in the perioperative period. METHODS: DailyMed website was searched using numerous terms for surgical disinfectants. Products used for health care worker handwashing/scrubbing or patient surgical cleansing/disinfecting were included. Each product's ingredients were recorded; those found on the 2017 American Contact Dermatitis Society (ACDS) Core Allergen Series were noted from each product. CONCLUSIONS: A total of 1940 products were identified, of which 267 were included in the analysis. A total of 66.3% contained iodine, 25.8% contained chlorhexidine digluconate, and 2.6% contained chloroxylenol. Within the group analyzed, 1586 ingredients were identified. Of these, 241 were ACDS Core Series allergens. Most products contained a single ACDS allergen. There were significant differences in allergens based on product type and active ingredient, with iodine-containing products having the fewest number of allergens. The most common ACDS allergens found were cocamide diethanolamide (22.5%), fragrance (21.7%), lanolin (19.5%), propylene glycol (6.7%), alkyl glucosides (6.0%), and sorbic acid derivatives (5.6%).


Assuntos
Alérgenos/efeitos adversos , Anti-Infecciosos Locais/efeitos adversos , Dermatite Alérgica de Contato/etiologia , Higienizadores de Mão/efeitos adversos , Procedimentos Cirúrgicos Operatórios , Anti-Infecciosos Locais/química , Clorexidina/efeitos adversos , Clorexidina/análogos & derivados , Dermatite de Contato/etiologia , Dermatite Ocupacional/etiologia , Desinfecção das Mãos , Higienizadores de Mão/química , Pessoal de Saúde , Humanos , Lanolina/efeitos adversos , Salas Cirúrgicas , Perfumes/efeitos adversos , Povidona-Iodo/efeitos adversos , Propilenoglicol/efeitos adversos , Xilenos/efeitos adversos
11.
Bull Exp Biol Med ; 167(6): 784-786, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31656000

RESUMO

Antibacterial activity of powdered preparations based on copper and silver nanoparticles was compared with activity of the reference preparation Baneocin on the model of local staphylococcal infection in white rats. The developed preparations exhibited pronounced antibacterial activity against methicillin-resistant S. epidermidis strains in vivo significantly (p<0.001) exceeding that of Baneocin, reduced microbial contamination of the wound on day 5 of study by 2 lg and more in comparison with bacterial load before treatment, and provided effective decontamination of the wound within 7-10 days.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus epidermidis/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Administração Tópica , Animais , Animais não Endogâmicos , Antibacterianos/administração & dosagem , Antibacterianos/química , Anti-Infecciosos Locais/química , Cobre/administração & dosagem , Cobre/química , Humanos , Nanopartículas Metálicas/química , Resistência a Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Ratos , Prata/administração & dosagem , Prata/química , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/microbiologia , Infecções Cutâneas Estafilocócicas/patologia , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia
12.
Int J Pharm ; 569: 118564, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31352049

RESUMO

Control of infection and inflammation is crucial for the success of periodontal treatment. In this study, in-situ forming implants (ISFI) loaded with chlorhexidine dihydrochloride (CHX) and ibuprofen (IBU) were developed and tested to optimize periodontal treatment outcomes. Release profiles were promising. Exposure to 1.5% and 5.3% CHX-IBU loaded ISFI's release media decreased significantly the P. gingivalis growth up to 20-fold and 35-fold, respectively, after 48 h (p < 0.05). The metabolic activity assay of gingival epithelial cells (EC) demonstrated 1.5% CHX-IBU-loaded ISFI to be non-toxic, therefore, it was selected for further experimentation. Furthermore, significant down-regulation of TNF-α release (34% at 6 h and 43% at 24 h, p < 0.05) in P. gingivalis lipopolysaccharide (Pg-LPS) stimulated EC exposed to 1.5% CHX-IBU ISFI release medium was demonstrated by ELISA. In vivo, 1.5% CHX-IBU ISFI was injected into the periodontal pocket in an experimental periodontitis mouse model and the reduction in inflammation and improvement in periodontal wound healing was evaluated through inflammatory cell scoring and histomorphometry at 7- and 15-days post-treatment. The results indicate that CHX-IBU loaded ISFI could be efficient as adjuvant to periodontal therapy for the control of infection and inflammation. Moreover, other (e.g., pro-regenerative) drugs could be incorporated into ISFI to further improve periodontal treatment outcomes.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Clorexidina/administração & dosagem , Ibuprofeno/administração & dosagem , Periodontite/tratamento farmacológico , Animais , Anti-Infecciosos Locais/química , Anti-Inflamatórios não Esteroides/química , Linhagem Celular , Clorexidina/química , Implantes de Medicamento , Liberação Controlada de Fármacos , Células Epiteliais/efeitos dos fármacos , Gengiva/citologia , Humanos , Ibuprofeno/química , Lipopolissacarídeos , Masculino , Camundongos Endogâmicos C57BL , Estudo de Prova de Conceito , Cicatrização/efeitos dos fármacos
13.
J Chem Inf Model ; 59(7): 3136-3143, 2019 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-31187992

RESUMO

Halogen bond interaction between a protein electronegative atom and a ligand halogen atom is increasingly attracting attention in the field of structure-based drug design. Nevertheless, gaps in understanding make it desirable to better examine the role of forces governing the formation of favorable halogen bond interactions, and the development of effective and efficient computational approaches to "design in" favorable halogen bond interactions in lead optimization process are warranted. Here, we analyzed the binding-site water properties of crystal structures with characterized halogen bond interactions between ligand halogen atoms and protein backbone carbonyl groups and, thus, found that halogen atoms involved in halogen bond interactions frequently replace calculated binding-site waters upon ligand binding. Moreover, we observed that the preferential directionality of halogen bond interactions aligns well with the orientations of these replaced waters, and these replaced waters exhibited differential energetic characteristics as compared to waters that are displaced by halogen atoms that do not form halogen bond interactions. Our discovery that replacement of calculated binding-site waters contributes to the formation of favorable halogen bond interactions suggests a practical approach for rational drug design utilizing halogen bond interactions with protein backbone carbonyl groups.


Assuntos
Proteínas/química , Água , Anti-Infecciosos Locais/química , Sítios de Ligação , Bases de Dados Factuais , Halogênios , Ligação de Hidrogênio , Modelos Moleculares , Ligação Proteica , Conformação Proteica , Triclosan/química
14.
Dokl Biochem Biophys ; 484(1): 48-51, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31012012

RESUMO

To select the optimum method for disinfecting scaffolds before recellularization, the effects of octenisept and chlorhexidine at different concentrations on lung biological matrices before and after decellularization were studied by using morphological methods (studies of biomechanical strength of extracellular matrix fibers) and by analyzing chemiluminescence in rats. Chlorhexidine diluted 1 : 10 had the least damage on the matrix properties and to the greatest extent contributed to disinfection of scaffolds for their further storage and experimental studies.


Assuntos
Anti-Infecciosos Locais/química , Clorexidina/química , Desinfecção/métodos , Matriz Extracelular/química , Pulmão/química , Animais , Ratos
15.
Plast Reconstr Surg ; 143(5): 1371-1382, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30807498

RESUMO

BACKGROUND: This study investigated whether a hyaluronic acid-povidone-iodine compound can enhance diabetic wound healing. METHODS: A dorsal skin defect (6 × 5 cm) in a streptozotocin-induced diabetes rodent model was used. Seventy male Wistar rats were divided into seven groups: I, normal control; II, diabetic control, no treatment; III, diabetic rats, lower molecular weight (100 kDa) hyaluronic acid; IV, rats, higher molecular weight (1000 kDa) hyaluronic acid; V, rats, 0.1% povidone-iodine; VI, rats, lower molecular weight hyaluronic acid plus povidone-iodine; and VII, rats, higher molecular weight hyaluronic acid plus povidone-iodine. Histologic examination was performed with hematoxylin and eosin staining. CD45, Ki-67, prolyl 4-hydroxylase, and vascular endothelial growth factor were evaluated with immunohistochemical staining. RESULTS: Compared with the control, higher molecular weight hyaluronic acid plus povidone-iodine-treated rats had significantly reduced wound area (p < 0.001). Higher molecular weight hyaluronic acid plus povidone-iodine increased wound healing time when compared with higher molecular weight hyaluronic acid, povidone-iodine, or lower molecular weight hyaluronic acid plus povidone-iodine. Histology revealed significantly increased neovessels and suppressed inflammatory response in the higher molecular weight hyaluronic acid plus povidone-iodine group when compared with the control group. Immunohistochemical staining revealed significantly increased Ki67, prolyl 4-hydroxylase, and vascular endothelial growth factor expression, and suppressed CD45 expression in the higher molecular weight hyaluronic acid plus povidone-iodine group when compared with the other groups. CONCLUSION: Higher molecular weight hyaluronic acid plus povidone-iodine complex dressing significantly facilitated diabetic wound healing via increasing neovascularization and tissue regeneration and suppressing a proinflammatory response.


Assuntos
Anti-Infecciosos Locais/farmacologia , Diabetes Mellitus Experimental/complicações , Ácido Hialurônico/farmacologia , Povidona-Iodo/farmacologia , Cicatrização/efeitos dos fármacos , Administração Cutânea , Animais , Anti-Infecciosos Locais/química , Anti-Infecciosos Locais/uso terapêutico , Bandagens , Diabetes Mellitus Experimental/induzido quimicamente , Pé Diabético/tratamento farmacológico , Pé Diabético/etiologia , Combinação de Medicamentos , Humanos , Ácido Hialurônico/química , Ácido Hialurônico/uso terapêutico , Masculino , Peso Molecular , Povidona-Iodo/química , Povidona-Iodo/uso terapêutico , Ratos , Ratos Wistar , Pele/efeitos dos fármacos , Pele/patologia , Estreptozocina/toxicidade , Resultado do Tratamento
16.
BMC Ophthalmol ; 19(1): 62, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30808316

RESUMO

BACKGROUND: Povidone-Iodine (PI) may be diluted when used as an antiseptic prior to an intravitreal injection in an attempt to decrease patient discomfort. This study aims to investigate the effect of diluting povidone-iodine (PI) on bacterial growth from bacterial droplet dispersal associated with speech. METHODS: Participants read a standardised script for 5 min over a blood agar plate positioned at 20 cm in a simulated position of an intravitreal injection procedure. The blood agar plates were subject to a randomised pre-application of 1% PI; 2.5% PI; 5% PI and no pre-application (control). The plates were incubated at 37 °C for 72 h and the number of Colony Forming Units (CFUs) was determined. CFUs were summarised as median and interquartile range (IQR). Wilcoxon rank sum test was used to assess pairwise comparisons of the various PI concentrations to the control group. Any trend across PI concentration was assessed using Kendall's tau rank correlation. RESULTS: Twenty-one subjects participated. Control plates had a median growth of 25 CFUs (interquartile range [IQR]:15-40), 1% PI plates had a median growth of 30 CFUs (IQR:15-82), 2.5% PI had a median growth of 18 CFUs (IQR:10-32) and 5% PI had a median growth of 2 CFUs (IQR:0-5). There was significantly less bacterial growth with 5% PI compared to control (P < 0.001). Bacterial growth at 2.5% PI and 1% PI did not differ significantly from control. There was a statistically significant trend for decreasing colony count as PI concentration increased (P < 0.001). CONCLUSIONS: PI concentrations less than 5% are not effective at reducing bacterial growth from bacterial droplet dispersal associated with speech. When using PI for pre-injection antisepsis, concentrations below 5% should be avoided.


Assuntos
Anti-Infecciosos Locais/farmacologia , Bactérias/efeitos dos fármacos , Infecções Oculares Bacterianas/prevenção & controle , Povidona-Iodo/farmacologia , Fala , Adulto , Anti-Infecciosos Locais/química , Contagem de Colônia Microbiana , Feminino , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Povidona-Iodo/química , Adulto Jovem
18.
Int J Nanomedicine ; 14: 289-300, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30643407

RESUMO

Background: Silver sulfadiazine (AgSD) is widely employed as an antibacterial agent for surface burn management. However, the antibacterial activity of AgSD was restrained because of the lower drug solubility and possible cytotoxicity. Objective: This study aimed to formulate stable silver sulfadiazine/nanosuspensions (AgSD/NSs) with improved AgSD solubility and prepare a suitable carrier for AgSD/NS delivery. Nanotechnology was used to overcome the low drug dissolution rate of AgSD, while the new carrier loaded with AgSD/NS was assumed to decrease the possible cytotoxicity, enhance antibacterial activity, and promote wound healing. Methods: AgSD/NSs were prepared by high pressure homogenization method. Poloxamer 407-based thermoresponsive hydrogels were prepared by cold method as carriers of AgSD/NS to obtain AgSD/NS-loaded thermoresponsive hydrogel. Scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) were used to measure the physicalchemical properties of AgSD/NSs and AgSD/NS-loaded gel. The cytotoxicity of the AgSD/NS-loaded gel was evaluated using methyl thiazolyltetrazolium assay with L929 mouse fibroblast cell lines. In vitro antibacterial activities of AgSD/NSs and AgSD/NS loaded gel were also measured. Results: Stable AgSD/NSs with an average particle size of 369 nm were formulated while 1.5% P407 was selected as a stabilizer. The optimized AgSD/NS thermoresponsive hydrogel exhibited the gelation temperature of approximately 30°C. A significant improvement in solubility was observed for AgSD nanoparticles (96.7%) compared with AgSD coarse powders (12.5%). The results of FTIR and XRD revealed that the physicochemical properties of AgSD/NS were reserved after incorporating into the hydrogel. The cell viability after incubation with AgSD/NS-loaded thermoresponsive hydrogel improved from 60.7% to 90.6% compared with incubation with AgSD/NS directly. Drug release profiles from the thermoresponsive hydrogel increased compared with the commercial AgSD cream, implying less application frequency of AgSD cream clinically. In vitro antibacterial studies manifested that AgSD nanocrystallization significantly enhanced the antibacterial activity compared with the AgSD coarse powder. Conclusion: The combination of AgSD nanosuspensions and thermoresponsive hydrogel effectively improved the AgSD antibacterial activity and decreased the cytotoxicity. This study also suggested that a poloxamer thermoresponsive hydrogel could be used as a delivery system for other nanocrystals to decrease possible nanotoxicity.


Assuntos
Antibacterianos/administração & dosagem , Bactérias/efeitos dos fármacos , Hidrogéis/administração & dosagem , Nanopartículas/administração & dosagem , Sulfadiazina de Prata/administração & dosagem , Temperatura , Administração Tópica , Animais , Antibacterianos/química , Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/química , Células Cultivadas , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Hidrogéis/química , Camundongos , Nanopartículas/química , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/metabolismo , Sulfadiazina de Prata/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/metabolismo
19.
J Biomol Struct Dyn ; 37(13): 3550-3565, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30189795

RESUMO

Triclocarban (TCC), as a broad spectrum antibacterial agent widely used in personal care products, has recently been recognized as environmental pollutant with the potential of adversely affecting wildlife and human health. However, the behavior of TCC in blood circulatory system and the potential toxicity of TCC at the molecular level have been poorly investigated. In this study, the effect of TCC on human serum albumin (HSA) and the binding mechanism of TCC to HSA were examined using spectroscopic techniques and molecular modeling methods. The fluorescence results suggested that the fluorescence of HSA was quenched by TCC through a static quenching mechanism and nonradiation energy transfer, and TCC was bound to HSA with moderately strong binding affinity via hydrophobic interaction based on the analysis of the thermodynamic parameters. The site marker competitive experiments revealed that TCC bound into subdomain IIA (site I) of HSA. In addition, the results obtained from the circular dichroism, Fourier transform infrared (FT-IR), 8-anilino-1-naphthalenesulfonic acid fluorescence, synchronous fluorescence, three-dimensional fluorescence spectra and dynamic light scattering suggested the change in the microenvironment and conformation of HSA during the binding reaction. Finally, the best binding mode of TCC and specific interaction of TCC with amino acid residues were determined using molecular docking and molecular dynamics simulations. In a word, the present studies can provide a way to help us well understand the transport, distribution and toxicity effect of TCC when it diffused in the human body. Communicated by Ramaswamy H. Sarma.


Assuntos
Carbanilidas/química , Carbanilidas/metabolismo , Modelos Moleculares , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Albumina Sérica Humana/química , Albumina Sérica Humana/metabolismo , Anti-Infecciosos Locais/química , Anti-Infecciosos Locais/metabolismo , Dicroísmo Circular , Humanos , Interações Hidrofóbicas e Hidrofílicas , Ligação Proteica , Conformação Proteica , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica
20.
Clin Infect Dis ; 69(1): 130-136, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-30281074

RESUMO

BACKGROUND: Central line-associated bloodstream infections (CLABSIs) often result from intraluminal microbial colonization and are associated with morbidity, mortality, and substantial costs. The use of antimicrobial catheter lock solutions may reduce the incidence of CLABSI. METHODS: Patients undergoing hemodialysis (HD) through a prevalent central venous catheter (CVC) were randomly assigned to have their CVC locked between dialysis sessions with an antimicrobial catheter lock solution that contained trimethoprim 5 mg/mL, ethanol 25%, and Ca-EDTA 3% (investigational medical device [IMD]) or heparin 5000 U/mL active control heparin (ACH). Exit site care was standardized by protocol-driven use of skin antiseptics and occlusive dressings. The composite primary endpoint consisted of the incidence of CLABSI and intracatheter thrombolytic treatment (TT). Given the viscosity and odor of the IMD, blinding was impossible. Therefore, a blinded endpoint committee adjudicated the incidence of CLABSI. RESULTS: A total of 270 patients on HD were enrolled and followed for 43738 CVC-days. Despite the low CLABSI incidence of 0.41/1000 CVC-days in patients randomized to ACH, the IMD further reduced the incidence 4.56-fold to 0.09/1000 CVC-days (P < .03). The product was well tolerated, and the frequency and severity of adverse events were comparable between groups. Intracatheter instillation of thrombolytics was more frequent in patients who received the IMD (12% ACH, 40% IMD; P < .001), but rates of catheter removal did not differ (13% ACH, 11% IMD). Overall, dialysis adequacy was comparable between groups. CONCLUSIONS: In patients on chronic HD, a trimethoprim, ethanol, and Ca-EDTA lock solution significantly reduced the incidence of CLABSI. CLINICAL TRIALS REGISTRATION: NCT01989091.


Assuntos
Bacteriemia/prevenção & controle , Infecções Relacionadas a Cateter/prevenção & controle , Cateteres , Ácido Edético/química , Etanol/química , Diálise Renal/instrumentação , Trimetoprima/química , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Infecciosos/química , Anti-Infecciosos Locais/química , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
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