Development of Chlorhexidine Digluconate and Lippia sidoides Essential Oil Loaded in Microemulsion for Disinfection of Dental Root Canals: Substantivity Profile and Antimicrobial Activity.

The dental intracanal disinfection is crucial to achieve the success of endodontic treatment, avoiding the maintenance of endodontic infections. Chlorhexidine digluconate can act as an irrigating agent for it. However, it can cause tissue irritation in high concentrations. Therefore, combinations with other antimicrobial agents and more efficient therapeutic alternatives are studied, which make it possible to administer drugs more safely and with minimal adverse effects. Thus, the objective of this study was the development of a microemulsion containing chlorhexidine digluconate and essential oil of Lippia sidoides to be used for disinfection of dental root canals and to evaluate its profile of substantivity and antimicrobial activity. The microemulsions were obtained through phase diagrams, using the spontaneous formation method. We completed a physical-chemical characterization and evaluate the stability of the microemulsions, in addition to the substantivity profile in a bovine root dentin model, and in vitro antibacterial effect on Enterococcus faecalis. A method for quantifying chlorhexidine was developed using UV-Vis spectroscopy. The microemulsions showed acid pH, conductivity above 1.3 µScm-1, and dispersion index similar to water. The microemulsions showed antimicrobial inhibition halos similar to the commercial gel conventionally used, but with four times more substantivity to dentinal tissues. Microemulsions were obtained as a therapeutic alternative to formulations available on the market, presenting themselves as a system with great potential for the administration of drugs for disinfection of root canals.

Amphotericin B-Loaded Emulgel: Effect of Chemical Enhancers on the Release Profile and Antileishmanial Activity In Vitro.

Cutaneous leishmaniasis is a neglected parasitic disease. Treatment is preferably performed with pentavalent antimony associated or not with amphotericin B (AmB). This study aimed to develop an emulgel with different chemical enhancers of cutaneous release. Initially, AmB emulsions were obtained with the chemical promoters, oleic acid and geraniol and without promoter, then for the evaluation of the formulations, a preliminary stability study was carried out where the formulations were submitted to centrifugation, before and after the freeze-thaw cycle and analyzed appearance, color, pH, spreadability, viscosity, conductivity, droplet size, assay, in vitro release study, in vitro antileishmania activity in Leishmania major promastigotes, and macrophage toxicity in the MTT test. The emulsions were yellowish, with no signs of instability after the centrifugation test. The pH range corresponded to that of the skin, which is 4.6 to 5.8, before and after the freeze-thaw cycle, the formulations had good spreadability and did not present significant viscosity differences before and after the freeze-thaw cycle, presenting a non-Newtonian characteristic. AmB content was within the kinetic model of zero order release, the formulation of 3% AmB and 5% oleic acid (formulation 1) was chosen to proceed with the antileishmania activity test and showed potential activity against the in vitro parasite with significant reduction of cytotoxicity on murine macrophages, indicating that the formulation is promising for the treatment of cutaneous leishmaniasis.

Emulgel based on amphotericin B and bacuri butter (Platonia insignis Mart.) for the treatment of cutaneous leishmaniasis: characterization and in vitro assays.

OBJECTIVE: This work aimed to develop and characterize a topical emulgel of amphotericin B (AmB) with bacuri butter (Platonia insignis Mart.) and evaluate its antileishmanial activity using in vitro assays. SIGNIFICANCE: Leishmaniasis is considered an infectious disease, with high incidence and capacity to produce deformities. The first-line treatment recommended by WHO, with pentavalent antimonials, is aggressive and very toxic. Therefore, the development of topical treatments can emerge as a promising and less offensive alternative. METHODS: The developed formulations were evaluated for organoleptic characteristics, centrifugation resistance, globule size, pH, electrical conductivity, viscosity, spreadability, drug content, preliminary stability, in vitro release profile, evaluation of antileishmanial activity using promastigotes forms of Leishmania major as infecting agents, macrophage cytotoxicity and selectivity index (IS). RESULTS: Formulated emulsions presented organoleptic characteristics compatible with its constituents; pH values were suitable for topical application, ranging from 4.73 to 5.02; introduced non-Newtonian shear thinning system; drug content was within the established standards, and the most suitable kinetic model of release was the first order. Regarding the in vitro assays, formulations containing both 1% and 3% of AmB presented similar outcomes, indicating a synergism between the bacuri butter and the drug, possibly showing a reduction on cytotoxicity to host cells. CONCLUSIONS: It was concluded that the formulations developed showed promising antileishmanial action and high potential for topical use.

Evaluation of the in vivo leishmanicidal activity of amphotericin B emulgel: An alternative for the treatment of skin leishmaniasis.

The American Cutaneous Leishmaniasis (ACL) is an infectious disease that can be fatal. The first line of treatment is pentavalent antimonies. However, due to its potential to develop resistance, Amphotericin B (AmB) started to be used as an alternative medicine. Current treatments are limited, a fact that has led to a growing interesting in developing new therapies. This study aims to evaluate the therapeutic potential in vivo of an amphotericin B + oleic acid (OA) emulgel in the treatment of cutaneous leishmaniasis in an experimental model. Strains of Leishmania major MHOM/IL/80/Friendlin of Leishmania major were used. The animals were inoculated subcutaneously. After the development of leishmanial, nodular or ulcerative lesions, the animals were divided into three groups (control, Group A and Group B) and treated twice a day for twelve days. The weight of the animals was measured and the size of the lesions was observed. A histopathological analysis was performed with skin fragments of lesions and with the spleen of animals treated with different treatments (emulgel, AmB 3% emulgel and AmB 3% plus OA 5% emulgel). It was observed that when subjected to treatment with AmB 3% emulgel during the study period using both formulations, with enhancer and without enhancer, ulcerative lesions regress gradually or even complete cure. The quantification of the average number of parasites recovered from the inoculation site was made after the treatment in each group and the differences were considered significant. The treatment with AmB 3% and OA 5% emulgel had the best in vivo therapeutic response, showing good prospects for cutaneous leishmaniasis therapy as an alternative therapy.

Films composed of white angico gum and chitosan containing chlorhexidine as an antimicrobial agent.

Anadenanthera colubrina, popularly known as white angico, is a species extensively cultivated in Brazil, mainly in the cerrado region, including the state of Piauí. This study examines the development of films composed of white angico gum (WAG) and chitosan (CHI) and containing chlorhexidine (CHX), an antimicrobial agent. The solvent casting method was used to prepare films. Different combinations and concentrations of WAG and CHI were used to obtain films with good physicochemical characteristics. Properties such as the in vitro swelling ratio, the disintegration time, folding endurance, and the drug content were determined. The selected formulations were characterised by scanning electron microscopy, Fourier-transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and X-ray diffraction, and the CHX release time and antimicrobial activity were evaluated. CHX showed a homogenous distribution in all CHI/WAG film formulations. The optimised films showed good physicochemical properties with 80% CHX release over 26 h, which is considered promising for local treatment of severe lesions in the mouth. Cytotoxicity tests of the films did not show toxicity. The antimicrobial and antifungal effects were very effective against the tested microorganisms.

Perfil de susceptibilidade aos carbapenêmicos de bacilos Gram-negativos fermentadores da glicose isolados de hemoculturas / Carbapenem susceptibility profile of Gram-negative glucose fermenting bacilli isolated from hemocultures

As Enterobacteriaceae são bactérias Gram-negativas e frequentes causadoras de infecções hospitalares. Os carbapenêmicos (CROs) são considerados as mais recentes linhas de defesa contra infecções por microrganismos multirresistentes, no entanto o desenvolvimento de bactérias multirresistentes a esta classe medicamentosa tem prejudicado o tratamento farmacológico. Nesse sentido, o presente estudo trata-se de uma análise retrospectiva, tendo como objetivo avaliar o perfil de resistência e susceptibilidade de bacilos Gram-negativos fermentadores da glicose aos carbapenêmicos em isolados de hemoculturas positivas no período de janeiro de 2018 a janeiro 2019. Das 5.733 hemoculturas realizadas nesse período, cerca de 5,4% (311 amostras) foram positivas. Dentre essas, 34,4% (107 amostras) positivas para enterobactérias e 65,6% (204 amostras) positivas para outras espécies. Foi observada uma maior incidência de Klebsiella pneumoniae (34,6% dos casos), seguido pela Klebsiella sp. (28,9%) e a Escherichia coli (26,2%). Contudo, três (03) isolados de hemocultura da espécie Klebsiella pneumoniae se mostraram resistentes aos três antibióticos (ertapenem, meropenem e imipenem). Dois isolados de Enterobacter cloaceae também obtiveram resistência aos antibióticos utilizados e uma espécie de Enterobacter aerogenes mostrou-se resistente apenas ao ertapenem e meropenem e sensibilidade ao imipenem.Enterobacteriaceae are Gram-negative bacteria and frequent causes hospital infections. Carbapenemic (CRO) are considered the latest lines of defense against infections by multidrug-resistant microorganisms, however the development of multidrug-resistant bacteria in this drug class has impaired treatment pharmacological. The present study is a retrospective analysis, with the objective of evaluating the resistance and susceptibility profile from isolates in blood cultures from January 2018 to January 2019, from positive blood cultures with enterobacteria growth and analysis of antibiograms performed from fermenter Gram-negative glucose bacilli to carbapenem antimicrobials. Of the 5,733 blood cultures performed from January 2018 to January 2019, about 5.4% (311 samples) were positive. Among these, 34.4% (107 samples) positive for enterobacteria and 65.6% (204 samples) for other species. A higher incidence of Klebsiella pneumoniae (34.6% of cases) was observed, followed by Klebsiella sp. (28.9%) and Escherichia coli (26.2%), however, three hemoculture isolates of the species Klebsiella pneumoniae, which were resistant to the three antibiotics (ertapenem, meropenem and imipenem). Two (2) isolates of Enterobacter cloaceae also obtained resistance to the antibiotics used and one (1) species of Enterobacter aerogenes proved resistant only to ertapenem and meropenem and sensitivity to imipenem.

As Enterobacteriaceae são bactérias Gram-negativas e frequentes causadoras de infecções hospitalares. Os carbapenêmicos (CROs) são considerados as mais recentes linhas de defesa contra infecções por microrganismos multirresistentes, no entanto o desenvolvimento de bactérias multirresistentes a esta classe medicamentosa tem prejudicado o tratamento farmacológico. Nesse sentido, o presente estudo trata-se de uma análise retrospectiva, tendo como objetivo avaliar o perfil de resistência e susceptibilidade de bacilos Gram-negativos fermentadores da glicose aos carbapenêmicos em isolados de hemoculturas positivas no período de janeiro de 2018 a janeiro 2019. Das 5.733 hemoculturas realizadas nesse período, cerca de 5,4% (311 amostras) foram positivas. Dentre essas, 34,4% (107 amostras) positivas para enterobactérias e 65,6% (204 amostras) positivas para outras espécies. Foi observada uma maior incidência de Klebsiella pneumoniae (34,6% dos casos), seguido pela Klebsiella sp. (28,9%) e a Escherichia coli (26,2%). Contudo, três (03) isolados de hemocultura da espécie Klebsiella pneumoniae se mostraram resistentes aos três antibióticos (ertapenem, meropenem e imipenem). Dois isolados de Enterobacter cloaceae também obtiveram resistência aos antibióticos utilizados e uma espécie de Enterobacter aerogenes mostrou-se resistente apenas ao ertapenem e meropenem e sensibilidade ao imipenem.