Experimental purulent corneal ulcer in rabbits as a model to study ocular dosage forms

Aim. The aim of this work was to develop experimental model of purulent corneal ulcer in rabbits for its application in the studies of ocular dosage forms. Methods. Rabbits body temperature was measured in three groups: (1) without corneal injury; (2) with the injury and formation of purulent ulcer, but without any therapy; (3) with the injury and formation of purulent ulcer, treated with ciprofloxacin. In parallel, swabs containing purulent discharge were taken for microbiological analysis. In the end of 10-days experiment rabbits (groups 2 and 3) were sacrificed; their corneas were extracted and analysed. Results. One day following the injury all rabbits had a purulent discharge, moderate eyelids edema and conjunctival hyperemia. Rabbits in groups 2 and 3 had a purulent corneal ulcer developed. The mean body temperature in group 1 was 38.6±0.1 °С; in group 2 it was 40.0±0.3 °С, in group 3 it was 39.1±0.3 °С. The levels of infection in group 2 in the beginning and on 10-th day of experiments were 1.0×107 colony forming units (CFU) and 4.3×106 CFU, respectively (not significant, p >0.1). In group 3 these levels were 1.0×107 CFU and 4.6×103 CFU, respectively (significant, p <0.0001). The histological investigation of enucleated eyes with corneal ulcers revealed the presence of edema, stratification, deep epithelial defects, endothelium desquamation, and corneal infiltration by neutrophils. Conclusion. Formation of a corneal ulcer leads to an increase in animal body temperature, which depends on timely therapy. Rectal temperature measurements in rabbits could serve as an easy parameter to follow the development of inflammation

In situ gelling systems based on Pluronic F127/Pluronic F68 formulations for ocular drug delivery

This study evaluated the use of Pluronic F127 and Pluronic F68 as excipients for formulating in situ gelling systems for ocular drug delivery. Thermal transitions have been studied in aqueous solutions of Pluronic F127, Pluronic F68 as well as their binary mixtures using differential scanning calorimetry, rheological measurements, and dynamic light scattering. It was established that the formation of transparent gels at physiologically relevant temperatures is observed only in the case of 20 wt % of Pluronic F127. The addition of Pluronic F68 to Pluronic F127 solutions increases the gelation temperature of binary formulation to above physiological range of temperatures. The biocompatibility evaluation of these formulations using slug mucosa irritation assay and bovine corneal erosion studies revealed that these polymers and their combinations do not cause significant irritation. In vitro drug retention study on glass surfaces and freshly excised bovine cornea showed superior performance of 20 wt % Pluronic F127 compared to other formulations. In addition, in vivo studies in rabbits demonstrated better retention performance of 20 wt % Pluronic F127 compared to Pluronic F68. These results confirmed that 20 wt % Pluronic F127 offers an attractive ocular formulation that can form a transparent gel in situ under physiological conditions with minimal irritation

Chitosan/poly(2-ethyl-2-oxazoline) films for ocular drug delivery: Formulation, miscibility, in vitro and in vivo studies

Polymeric films were prepared based on chitosan and its blends with poly(2-ethyl-2-oxazoline) by casting from aqueous solutions. These materials were characterised using a number of physicochemical techniques, including Fourier-transform infrared spectroscopy, thermal gravimetric analysis, differential scanning calorimetry, wide angle x-ray diffraction, tensile testing and scanning electron microscopy. All these studies indicate that there is a weak intermacromolecular hydrogen bonding between these polymers, which facilitates their complete miscibility in solid state. These films were formulated with sodium fluorescein as a model drug and were evaluated for their potential application in ocular drug delivery both in vitro and in vivo. It was established that the films are biocompatible and mucoadhesive; they are capable of providing a sustained drug release when administered topically on the cornea