Desenvolvimento e avaliação da atividade anti-inflamatória de filmes poliméricos de quitosana contendo pentoxifilina para uso tópico

Abstract

Films are an important system to distribute medicines. They allow these substances to be carried and liberated at the target site. Pentoxifylline is a potent vasodilator that reports pleiotropic effects as anti-inflammatory activity. The aim of this study was to develop, characterize and evaluate the anti-inflammatory activity of chitosan films containing Pentoxifylline for topical use. The sol-gel method was used to produce the films and prepare a chitosan 1% solution with pentoxifylline (10 and 20 mg/mL). The solution was added in Petri dishes and subjected to homogenization and drying in an oven, resulting in the films. The films were characterized by Fourier transform infrared (FTIR), X-ray Diffraction (XRD), Thermogravimetry (TG), Differential Scanning Calorimetry (DSC) Exploratory and scanning electron microscopy (SEM). The release profile of Pentoxifylline from this system was assessed and the in vivo study was conducted to evaluate the anti inflammatory activity and possible antimicrobial activity of the films. The color of the films ranged from transparent (FBr) to milky yellow (F1 and F2). In the characterization in FTIR, F1 and F2 presented bands characteristics of Pentoxifylline and Chitosan; similar bands of the FBr presented Chitosan. In the DRX, Pentoxifylline showed a crystalline profile, F1 and F2 were partially amorphous, while FBR behaved completely amorphous. In the DSC, pentoxifylline presented an endothermic peak at 105.11° C and Chitosan presented an endothermic peak at 96.12° C and an exothermic at 306.29° c. The physical mixture of powder has shown endothermic peaks at 88.55 °C and 134.78°C and an exothermic peak at 308.15°c. F1 presented an endothermic peak at 118.69° C and an exothermic peak at 285.59° c. F2 presented endothermic peaks at 78.07° C and 122.05° C and an exothermic peak at 286.73°c. In the SEM, the Pentoxifylline presented a heterogeneous morphology. F1 and F2 movies showed homogeneous morphology and could confirm the encapsulation in the system. The in vitro release study of films followed the kinetic model of Higuchi. The films released F1 (82%) and F2 (88%) at the end of the study, showing a controlled release and the formation of a plateau. In the in vivo study, the animals treated with F2 showed a significant difference in healing at the day 4 for all other groups. On the 6th day, it was observed a significant difference in relation to F2 compared to the FBr, F1, and ointment. The ointment group presented a different profile from other treatments and a difference in the healing process during all days of the study. On the 9th day of treatment, the group treated with F2 complete closure of the lesion presented while the remaining groups presented the injury in about 20% of the original size. The microbiological study, treatment with FBr was possible to observe that Enterobactergergoviae, Citrobacterfreundiie Escherichia coli were inhibited, but Staphylococcus aureus and Hafnia alvei were present in a mouse. In the group treated with F2 there was inhibition of Escherichia coli Enterobacteraerogenese and Staphylococcus aureus inhibition in just one animal. Thus, the present study developed films present efficient encapsulation of the drug in the system, and a very interesting release profile, as well as demonstrated very promising for acceleration in the healing process of injuries, because your proven anti-inflammatory activity in vivo study, and a satisfactory activity front the strains of bacteria that colonized the lesion.