RESUMO
People with weakened immune systems are at risk of developing candidiasis which is a fungal infection caused by several species of Candida genus. In this work, polymeric nanoparticles containing miconazole nitrate and the anesthetic lidocaine clorhydrate were developed. Miconazole was chosen as a typical drug to treat buccopharyngeal candidiasis whereas lidocaine may be useful in the management of the pain burning, and pruritus caused by the infection. Nanoparticles were synthesized using chitosan and gelatin at different ratios ranging from 10:90 to 90:10. The nano-systems presented nanometric size (between 80 and 300 nm in water; with polydispersion index ranging from 0.120 to 0.596), and positive Z potential (between 20.11 and 37.12 mV). The determined encapsulation efficiency ranges from 65 to 99% or 34 to 91% for miconazole nitrate and lidocaine clorhydrate, respectively. X-ray diffraction and DSC analysis suggested that both drugs were in amorphous state in the nanoparticles. Finally, the systems fitted best the Korsmeyer-Peppas model showing that the release from the nanoparticles was through diffusion allowing a sustained release of both drugs and prolonged the activity of miconazole nitrate over time against Candida albicans for at least 24 h.
Assuntos
Candida albicans/isolamento & purificação , Candidíase/tratamento farmacológico , Lidocaína/administração & dosagem , Miconazol/administração & dosagem , Nanopartículas/química , Polímeros/química , Antifúngicos/administração & dosagem , Antifúngicos/química , Varredura Diferencial de Calorimetria , Quitosana , Humanos , Lidocaína/química , Miconazol/química , Nanopartículas/administração & dosagem , Difração de Raios XRESUMO
Oropharyngeal candidiasis is a recurrent oral infection caused by Candida species. Gel formulation containing miconazole nitrate is the most common approach for treating oral candidiasis. However, traditional oral topical antifungal therapies have many limitations, including short contact time with the oral mucosa and the necessity to administrate various doses per day. Thus, the aim of this work was to formulate composited microparticulated systems based on combinations of mucoadhesive cationic, anionic, and nonionic polymers that could protect and modify the drug release rate and therefore avoid a fast dilution of the drug by saliva. Microparticulated systems were prepared by the spray drying method employing chitosan, gelatin, and hydroxypropyl methylcellulose. The morphology of the systems was investigated by scanning electron microscopy; drug crystallinity was studied by X-ray, while interactions between polymers were analyzed by infrared spectroscopy. Drug release and halo zone test were employed to analyze the release and activity of the systems loaded with miconazole against Candida albicans cultures. The most appropriate microparticulated system was the one based on chitosan and gelatin which showed homogeneous morphology (mean size of 1.7 ± 0.5 µm), a protective effect of the drug, and better antifungal effect against Candida culture than miconazole nitrate and the other assayed systems. Taking into account these results, this approach should be seriously considered for further evaluation of its safety and in vivo efficacy to be considered as an alternative therapeutic system for the treatment of oral candidiasis.
Assuntos
Antifúngicos/química , Miconazol/química , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Quitosana/química , Composição de Medicamentos , Miconazol/farmacologia , Polímeros/químicaRESUMO
Numerous films with a dissolved or dispersed active principle within a polymeric matrix have been described in literature. However, the incorporation of solid crystals into the films may influence several relevant properties. Additionally, it has been reported that different polymeric matrices lead to films presenting a different performance. The aim of this work was to evaluate the effect of the combination of chitosan with carrageenan (κ-, λ-, and ι-) as matrices, and of the miconazole nitrate incorporation method, on the films behavior. Mechanical properties, drug release and antifungal activity were evaluated. The state of the drug in the films was analyzed by different techniques. Films showed a homogeneous surface and a thermal protective effect on the drug. The combination of chitosan and λ-carrageenan leads to films with the highest values of tensile and mucoadhesive strength. Films with solubilized drug displayed slightly higher elongation at break, tensile and mucoadhesive strength and faster drug release than those with suspended miconazole nitrate. However, no differences were found regarding the antifungal activity of the different formulations including time-to-kill curves.
Assuntos
Antifúngicos/administração & dosagem , Carragenina/administração & dosagem , Química Farmacêutica/métodos , Quitosana/administração & dosagem , Miconazol/administração & dosagem , Adesividade , Administração Bucal , Antifúngicos/química , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Carragenina/química , Quitosana/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Miconazol/química , Resistência à TraçãoRESUMO
Oral candidiasis is the most common opportunistic infection affecting patients with the human immunodeficiency virus. Miconazole buccal tablets or miconazole gel are approved for the treatment of oropharyngeal candidiasis. However, buccal films present more flexibility and also offer protection for the wounded mucosa, reducing pain. Due to their small size and thickness, buccal films may improve patients' compliance, compared to tablets. Additionally, they may increase the relatively short residence time on the mucosa of oral gels, which are easily removed by saliva. Polymeric films loaded with miconazole nitrate were prepared by a casting/solvent evaporation methodology using chitosan, carbopol, gelatin, gum arabic, and alginate to form the polymeric matrices. The morphology of films was investigated by scanning electron microscopy; interactions between polymers were analyzed by infrared spectroscopy and drug crystallinity by differential thermal analysis and X-ray diffraction. Films were characterized in terms of thickness, folding endurance, tensile properties, swelling, adhesiveness, and drug release. Finally, the antifungal activity against cultures of the five most important fungal opportunistic pathogens belonging to Candida genus was investigated. The more appropriate formulations were those based on chitosan-gelatin and chitosan-carbopol which showed good mechanical properties and adhesiveness, a relative low swelling index, improved drug release, and showed better in vitro activity against Candida cultures than miconazole nitrate raw material. Thus, it will be possible to produce a new pharmaceutical form based on polymeric films containing chitosan and miconazole nitrate, which could be loaded with low drug concentration producing the same therapeutic effect against Candida cultures.
Assuntos
Antifúngicos/química , Adesividade , Química Farmacêutica , Miconazol , Polímeros , Difração de Raios XRESUMO
In this work, chitosan films were prepared by a casting/solvent evaporation methodology using pectin or hydroxypropylmethyl cellulose to form polymeric matrices. Miconazole nitrate, as a model drug, was loaded into such formulations. These polymeric films were characterized in terms of mechanical properties, adhesiveness, and swelling as well as drug release. Besides, the morphology of raw materials and films was investigated by scanning electron microscopy; interactions between polymers were analyzed by infrared spectroscopy and drug crystallinity studied by differential scanning calorimetry and X-ray diffraction. In addition, antifungal activity against cultures of the five most important fungal opportunistic pathogens belonging to Candida genus was investigated. Chitosan:hydroxypropylmethyl cellulose films were found to be the most appropriate formulations in terms of folding endurance, mechanical properties, and adhesiveness. Also, an improvement in the dissolution rate of miconazole nitrate from the films up to 90% compared to the non-loaded drug was observed. The in vitro antifungal activity showed a significant activity of the model drug when it is loaded into chitosan films. These findings suggest that chitosan-based films are a promising approach to deliver miconazole nitrate for the treatment of candidiasis.
Assuntos
Candidíase Bucal/tratamento farmacológico , Quitosana , Sistemas de Liberação de Medicamentos , Derivados da Hipromelose/farmacologia , Miconazol , Adesividade , Administração Bucal , Antidiarreicos/química , Antidiarreicos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Quitosana/química , Quitosana/farmacologia , Composição de Medicamentos , Humanos , Miconazol/química , Miconazol/farmacologia , Microscopia Eletrônica de Varredura/métodos , Pectinas/química , Pectinas/farmacologia , Polímeros/farmacologia , Difração de Raios X/métodosRESUMO
Se estudió la eficacia y tolerancia del clorhidrato de prazosina en 192 pacientes, 90 hombres, 102 mujeres cuyas edades variaron entre 29 y 65 años portadores de HAE en 10 hospitales de Lima metropolitana y 1 de provincias agrupados en 3 categorías según los criterios de la OMS - 1962. Después de 1 semana de placebo se hicieron controles de presión arterial (PA) supina cardíaca (FC) al finalizar la 1ra., 2da., 4ta., 6ta., 8va. semana. La dosis fue de 0.5 mg b.i.d. tomando la primera al acostarse. A juicio del investigador y a partir de la 6ta. semana se añadió un diurético (52 casos la mayoría usó clortalidona, o hidroclorotiazida y sólo 4 casos furosemida. al finalizar la 8va. semana se encontró una respuesta "normalizada" (PAD 90 mmHg) en 100% de los hipertensos leves, 85% de los moderados y 60% de los severos, y una respuesta "satisfactoria" (PAD 100 mmHg) en 98% de los hipertensos moderados y en 90% de severos. Los efectos más frecuentes fueron: cefalea, mares y palpitaciones. No se observó ningún caso de "fenómeno de la primera dosis". De acuerdo al estudio, la prazosina es una droga útil en el tratamiento de la HAE cualquiera sea su severidad, teniendo en cuenta su baja toxicidad, su amplio rango de sodificación y su potenciación combinada con diuréticos. Si a esto le agregamos su carencia de "fenómeno de rebote" y de efectos sobre la líbido, así como su favorable acción sobre las dislipoproteinas al elevar el HDL. Se concluye que la prazosina es una droga con amplias ventajas en el manejo de los hipertensos