Spiramyin-loaded PLGA implants for the treatment of ocular toxoplasmosis: development, characterization, biocompatibility, and anti-toxoplasma activity.

Ocular toxoplasmosis is the major cause of infectious posterior uveitis worldwide, inducing visual field defect and/or blindness. Despite the severity of this disease, an effective treatment is still lacking. In this study, spiramycin-loaded PLGA implants were developed aiming at the treatment of ocular toxoplasmosis. Implants were manufactured by a hot-molding technique, characterized by Fourier Transform Infrared Spectroscopy, X-Ray Diffraction, Differential Scanning Calorimetry, Scanning Electron Microscopy; evaluated in terms of ocular biocompatibility by immunofluorescence, flow cytometry, cell migration, Hen's egg test-chorioallantoic membrane (HET-CAM) irritation test; and investigated in terms of in vitro efficacy against Toxoplasma gondii . Characterization techniques indicated that spiramycin was dispersed into the polymeric chains and both substances preserved their physical structures in implants. The HET-CAM test indicated that implants did not induce hemorrhage or coagulation, being non-irritant to the CAM. ARPE-19 cells showed viability by MTT assay, and normality in cell cycle kinetics and morphology, without stimulating cell death by apoptosis. Finally, they were highly effective against intracellular parasites without inducing human retinal pigment epithelial cell death. In conclusion, spiramycin-loaded PLGA implants represent a promising therapeutic alternative for the local treatment of ocular toxoplasmosis.

Antiangiogenic activity of a bevacizumab-loaded polyurethane device in animal neovascularization models.

PURPOSE: To evaluate the antiangiogenic activity of bevacizumab-loaded polyurethane using two animal models of neovascularization. METHODS: The percentage of blood vessels was evaluated in a chicken chorioallantoic membrane model (n=42) and in the rabbit cornea (n=24) with neovascularization induced by alkali injury. In each model, the animals were randomly divided into the groups treated with the bevacizumab-loaded polyurethane device, phosphate-buffered-saline (negative control) and bevacizumab commercial solution (positive control). Clinical examination, as well as histopathological and immunohistochemical evaluation, were performed in the rabbit eyes. Microvascular density in hot spot areas was determined in semi-thin sections of corneal tissue by hematoxylin-eosin staining and factor VIII immunohistochemistry. Immunohistochemical analysis was also performed to evaluate VEGF expression. RESULTS: In the evaluated models, the use of bevacizumab (Avastin®) and the bevacizumab-loaded polyurethane device led to similar results with regard to inhibition of neovascularization. In the chorioallantoic membrane model, the bevacizumab-loaded polyurethane device reduced angiogenesis by 50.27% when compared to the negative control group. In the rabbit model of corneal neovascularization, the mean density of vessels/field was reduced by 46.87% on analysis of factor VIII immunohistochemistry photos in the bevacizumab-loaded polyurethane device group as compared to the negative control (PBS) sections. In both models, no significant difference could be identified between the bevacizumab-loaded polyurethane device and the positive control group, leading to similar results with regard to inhibition of neovascularization. CONCLUSIONS: The present study shows that the bevacizumab-loaded polyurethane device may release bevacizumab and inhibit neovascularization similarly to commercial bevacizumab solution in the short-term.

Papain wound dressings obtained from poly(vinyl alcohol)/calcium alginate blends as new pharmaceutical dosage form: Preparation and preliminary evaluation.

Transparent, soft, flexible, mechanically resistant films, which are ideal for use as wound dressings were prepared in the presence of 2% papain, a proteolytic enzyme that can play a role in the chemical debridement of the skin and can accelerate the healing process. The films, based on poly(vinyl alcohol):calcium alginate blends with increasing concentrations of polysaccharide (10, 20, and 30% v/v), were obtained by casting method. FTIR and DSC analyses were performed to assess the composition and miscibility of blends. Mechanical properties such as tensile strength, elasticity modulus, and elongation at breakpoint were evaluated. The influence of different concentrations of calcium alginate on physical attributes of films like wettability, swelling capacity and mechanical properties was determined. The stability of papain in the films was assessed indirectly by hemolytic activity assay employing direct contact method and confirmed by technique based on blood agar diffusion. Preliminary cytotoxicity was evaluated with the XTT method. The results showed that at the polymer concentrations tested, the blends were miscible. The increase in the content of the calcium alginate increased the wettability and swelling capacity of the films, which is desirable in wound dressings. On the other hand, mechanical resistance decreased without causing breakage of the films during the swelling tests. The hemolytic activity of the films was maintained during the studied period, suggesting the stability of papain in the proposed formulations. Cellular viability indicated that the films were non-toxic. The analysis of the results showed that it is possible to prepare interactive and bioactive wound dressing containing papain from blends of PVA and calcium alginate polymers.