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.

PLGA Implants containing vancomycin and dexamethasone: development, characterization and bactericidal effects.

Post-operative endophthalmitis is an infection and an inflammation of the eye following a surgical procedure. Its treatment is based on drug injections into the eye. However, this treatment can lead to ocular complications. Intraocular implants could substitute the conventional therapy. Poly(lactic-co-glycolic acid) (PLGA) implants comprising on vancomycin and dexamethasone were evaluated as drug delivery system to treat endophthalmitis after cataract surgery. Implants were characterized by drug content uniformity, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Wide Angle X-ray Scattering (WAXS), Scanning Electron Microscopy (SEM) and in vitro drug release. The bactericidal effect of vancomycin, eluted from the implants, was demonstrated against Staphylococcus aureus and Staphylococcus epidermidis. The drugs were uniformly distributed in the polymer. The analytical techniques revealed the chemical integrity of the drugs incorporated into the polymer and the modification of dexamethasone semi-crystalline nature. Drugs were controlled released from implants; and the eluted vancomycin showed bactericidal effects. In conclusion, PLGA implants containing vancomycin and dexamethasone may represent a therapeutic alternative to treat post-operative endophthalmitis.

Analysis of acyclovir in vitreous humor by a validated HPLC method.

An HPLC-UV method was developed and validated for the determination of acyclovir in vitreous humor. The method was carried out in isocratic mode using 0.02 mol/L acetic acid/methanol (95:5) as mobile phase, a C18 column at 25 degrees C and UV detection at 254 nm. The method was linear (r2> 0.99) over the range of 35-700 microg/mL, precise (RSD <5%), accurate (recovery ranged from 98.18 to 99.64%), robust, selective regarding of the vitreous humor, and robust remaining unaffected by deliberate variations in relevant parameters. The validated HPLC-UV method can be successfully applied to determine acyclovir directly injected into the vitreous cavity of rabbits' eye.

Safety and pharmacokinetics of an intravitreal biodegradable implant of dexamethasone acetate in rabbit eyes.

The treatment of vitreoretinal diseases is limited and, nowadays, new drug delivery approaches have been reported in order to increase drug bioavailability. The objective of the current study was to determine the pharmacokinetic profile of a biodegradable dexamethasone acetate implant inserted into the vitreous of rabbits and to evaluate its potential signs of toxicity to the rabbits' eyes. The results showed that the intravitreous drug concentration remained within the therapeutic range along the 8-week period of evaluation. The system under study was not toxic to the normal rabbit retina, and no significant increase in intraocular pressure was observed.

Encapsulation of insulin-cyclodextrin complex in PLGA microspheres: a new approach for prolonged pulmonary insulin delivery.

The insulin administration by pulmonary route has been investigated in the last years with good perspectives as alternative for parenteral administration. However, it has been reported that insulin absorption after pulmonary administration is limited by various factors. Moreover, in the related studies one daily injection of long-acting insulin was necessary for a correct glycemic control. To abolish the insulin injection, the present study aimed to develop a new formulation for prolonged pulmonary insulin delivery based on the encapsulation of an insulin:dimethyl-beta-cyclodextrin (INS:DM-beta-CD) complex into PLGA microspheres. The molar ratio of insulin/cyclodextrin in the complex was equal to 1:5. The particles were obtained by the w/o/w solvent evaporation method. The inner aqueous phase of the w/o/w multiple emulsion contained the INS:DM-beta-CD complex. The characteristics of the INS:DM-beta-CD complex obtained were assessed by 1H-NMR spectroscopy and Circular Dichroism study. The average diameter of the microspheres prepared, evaluated by laser diffractometry, was 2.53 +/- 1.8 microm and the percentage of insulin loading was 14.76 +/- 1.1. The hypoglycemic response after intratracheal administration (3.0 I.U. kg(-1)) of INS:DM-beta-CD complex-loaded microspheres to diabetic rats indicated an efficient and prolonged release of the hormone compared with others insulin formulations essayed.