RESUMO
Inclusions of lidocaine hydrochloride in cyclodextrins were prepared to obtain stable complexes compatible for association with chlorhexidine in a new gel formulation for use in urogenital applications. Two cyclodextrins, ß-cyclodextrin and methyl-ß-cyclodextrin, were used for encapsulating lidocaine hydrochloride through solubilization and kneading techniques. The lidocaine-cyclodextrin complexes were characterized by ultraviolet spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction. The results revealed that the techniques generated good yields of inclusion products that maintained the functional properties of lidocaine. In addition, the inclusion products obtained improved the compatibility of lidocaine hydrochloride with chlorhexidine in solution and a gel formulation. The gel formulation displayed desirable rheological and physicochemical properties. The results presented here are the first description of the inclusion of lidocaine with cyclodextrins, which improves compatibility with chlorhexidine in formulations for simultaneous delivery.
Assuntos
Clorexidina/análogos & derivados , Ciclodextrinas/química , Géis/química , Lidocaína/química , Análise de Variância , Clorexidina/química , Clorexidina/farmacocinética , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Módulo de Elasticidade , Lidocaína/farmacocinética , Modelos Lineares , Modelos Biológicos , Reprodutibilidade dos Testes , Cremes, Espumas e Géis Vaginais/química , ViscosidadeRESUMO
Schistosomiasis is one of the most prevalent infectious diseases worldwide and classified as a neglected disease for which there is an urgent need for searching new drug candidates. According to TDR/WHO, existing leads with proven schistosomicidal activity, like meclonazepam, might be the objects of further exploration. Here, we decided to investigate if the benzodiazepine binding sites that we recently characterized in adult Schistosoma mansoni could represent the molecular target of meclonazepam for its effect on worm motility and morphological appearance. The EC(50) of meclonazepam for its contracturant effect is 10-20 times lower than its IC(50) for binding to the worm benzodiazepine binding sites. On the contrary, benzodiazepines like flunitrazepam and diazepam have affinities at least 50 times higher than meclonazepam for these binding sites but did not induce contraction of the worms. We also confirmed the existence of a great similarity between the appearance, kinetics, Emax and external calcium dependency of the contractile effect of praziquantel and meclonazepam. Based on computer-aided molecular modeling calculations, we verified that a certain structural similarity exists between the active enantiomers of both drugs. We further proposed the hypothesis of common pharmacophoric elements including amide and imine subunits and the asymmetric carbons of S-(+)-meclozepam and R-(-)-praziquantel. As a whole, the present data indicate that the contracturant effect of meclonazepam is not a result of its binding to the worm benzodiazepine binding sites but that it shares some basic transduction pathway with praziquantel, even if not through identical molecular targets or binding sites.