Metronidazole thermogel improves retention and decreases permeation through the skin

ABSTRACT Metronidazole (MTZ) is widely used as the standard antibiotic for the treatment of rosacea and, more recently, is being used off label in Brazilian hospitals for the treatment of wounds. Following oral administration, minimal amounts of active agent reaches the skin and side effects are strongly induced. Consequently, MTZ is currently being applied topically in order to improve the therapeutic efficacy with reduced side effects, with Rozex(r) (RZ) (an MTZ gelled formulation) being the only marketed product. This study examined whether the use of MTZ 0.75% from thermogel formulations could improve drug retention and reduce dermal exposure compared to that by Rozex(r). Following a 21 h permeation study, the highest total amount of MTZ permeated through the rat healthy and disturbed skin was seen with Rozex(r), but similar to all formulations regardless of the skin condition. On the other hand, the amount retained in the epidermis/dermis was larger for thermogel formulations; at least 4 fold that of Rozex(r), when the stratum corneum was present as a barrier. In conclusion, thermogel formulations can be favorable alternatives to Rozex(r) for the topical application of MTZ with improved efficacy and reduced side effects.

Efecto del metronidazol suplementado con hidroquinona en la adherencia de Lactobacillus acidophilus en células vaginales ovinas / Effect of metronidazole supplemented with hydroquinone on the adhesion of Lactobacillus acidophilus in ovine vaginal cells

This work demonstrates that the addition of metronidazole together with a ubiquitous quinone compound reduces adherence of Lactobacillus acidophilus to ovine vaginal cells. Spectrophotometric and voltammetric studies have shown that neoformed compounds were observed in these systems; there were also changes in their electroactive composition, and the oxidant status had a significantly higher value compared to the control (p < 0.05). Based on reduction potential (E; mV), the distribution of electroactive compound concentrations suggests that the compounds with low reduction potential induce this behavior, which would indicate that the addition of metronidazole with a ubiquitous quinone compound to the vaginal system might increase the reductive capacity of these systems. This work shows that the study of behavior and fluctuations of the redox compounds that compose the vaginal environment, in terms of concentration and species of redox molecules, must be hierarchized in order to better understand the early stages of colonization by microorganisms.

Este trabajo demuestra que la incorporación de metronidazol conjuntamente con un compuesto quinónico ubicuo disminuye la adherencia de Lactobacillus acidophilus a células vaginales ovinas. Los estudios espectrofotométricos y voltamétricos mostraron que en estos sistemas aparecieron compuestos neoformados y que hubo modificaciones en la composición electroactiva; asimismo, el estatus oxidante presentó un valor significativamente superior con respecto al control (p < 0,05). Según los potenciales de reducción (E; mV), la distribución de las concentraciones de los compuestos electroactivos muestra que los compuestos con bajos potenciales de reducción inducen este comportamiento. Esto indicaría que la incorporación de esta mezcla al sistema vaginal aumentaría su capacidad reductora. El trabajo muestra que el estudio del comportamiento y las fluctuaciones de los compuestos redox que componen el ambiente vaginal, en términos de concentración y especies moleculares, debe ser jerarquizado para comprender mejor las primeras etapas de la colonización de este ambiente por parte de los microorganismos.

Metronidazole-containing gel for the treatment of periodontitis: an in vivo evaluation

The aim of this investigation was to monitor metronidazole concentrations in the gingival crevicular fluid (GCF) collected from periodontal pockets of dogs after treatment with an experimental 15 percent metronidazole gel. Five dogs had periodontitis induced by cotton ligatures placed subgingivally and maintained for a 30-day period. After the induction period, only pockets with 4 mm or deeper received the gel. Each pocket was filled up to the gingival margin by means of a syringe with a blunt-end needle. GCF was collected in paper strips and quantified in an electronic device before and after 15 minutes, 1 h, 6 h, 24 h and 48 h of gel administration. The GCF samples were assayed for metronidazole content by means of a high performance liquid chromatography method. Concentrations of metronidazole in the GCF of the 5 dogs (mean ± SD, in µg/mL) were 0 ± 0 before gel application and 47,185.75 ± 24,874.35 after 15 minutes, 26,457.34 ± 25,516.91 after 1 h, 24.18 ± 23.11 after 6 h, 3.78 ± 3.45 after 24 h and 3.34 ± 5.54 after 48 h. A single administration of the 15 percent metronidazole gel released the drug in the GCF of dogs in levels several-fold higher than the minimum inhibitory concentration for some periodontopathogens grown in subgingival biofilms for up to one hour, but metronidazole could be detected in the GCF at least 48 hours after the gel application.

Estudo da pasta de metronidazol, lidocaína e ascorbosilane C sobre o processo de reparo de alvéolos dentais infectados em ratos / Effect of metronidazole, lidocaine and ascorbosilane C paste on delayed healing of wound extraction in rats

O processo de reparo do alvéolo infectado de ratos foi avaliado após a limpeza cirúrgica e irrigaçäo com soro fisiológico, seguida do preenchimento da loja com uma pasta composta por metronidazol, lidocaína e ascorbosilane C. Para tanto, foram extraídos os incisivos centrais superiores direitos de todos os animais e provocada alveolite naqueles dos grupos 2 (alveolite sem tratamento) e 3 (alveolite tratada). No Grupo 1, foi analisado o reparo normal. Os animais, em número de cinco em cada grupo, foram sacrificados aos seis, 15 e 28 dias pós-operatórios e as peças obtidas processadas para análise histológica. Com base nos resultados, foi possível concluir que a pasta constituída por metronidazol a 10 por cento, lidocaína a 2 por cento, carboximetilcelulose, menta e ascorbosilane C a 5 por cento näo interferiu na cronologia normal do processo de reparo em alvéolos dentais infectados de ratos, evidenciando comportamento similar àquele apresentado pelo Grupo Controle

Influência da pasta à base de metronidazol a 10 por cento e lidocaína a 2 por cento sobre o processo de reparo em alvéolo dental infectado: análise histológica e histométrica em ratos / The influence of the ointment compounded by 10 per cent of metronidazole and 2 per cent of lidocaine over delayed healing of wound extraction: a histological and histometric analysis in rats

O processo de reparo do alvéolo infectado de ratos (Rattus norvegicus, albinus, Wistar) foi avaliado após a limpeza cirúrgica e irrigaçäo com soro fisiológico, seguida do preenchimento da loja com uma pasta à base de metronidazol a 10 por cento e lidocaína a 2 por cento. Os 75 ratos experimentais constituíram os seguintes grupos: I.Controle (reparo normal); II.Alveolite sem tratamento; III.Limpeza cirúrgica e irrigaçäo; IV. Metronidazol a 10 por cento, lidocaína 2 por cento, menta e lanolina (pasta A); V.Metronidazol a 10 por cento, lidocaína a 2 por cento, menta e carboximetilcelulose (pasta B). Os animais, em número de cinco em cada grupo, foram sacrificados aos 6, 15 e 28 dias pós-operatórios e as peças obtidas foram analisadas através de microscopia óptica. Os resultados foram submetidos a análise qualitativa e quantitativa e, com base nos achados, foi possível concluir que a composiçäo proposta neste estudo apresentou resultados que indicam a sua aplicaçäo em alvéolos acometidos por alveolite, constituindo-se segura opçäo para o controle de täo desconfortável patologia