Versatile time-release technology reducing frequency of invasive injections in treating retinal diseases

Abstract

Purpose: To design a controlled release system capable of prolong effective therapeutic agents against chronic eye diseases by intravitreal injection.

Methods: In this study we report that a versatile drug delivery platform, namely BioSeizer, prolong effective therapeutic agents against chronic ocular diseases. This technology is directly applicable to existing drug products through a modified dehydration-rehydration vesicles (DRV) method. A small molecule drug dexamethasone sodium phosphate (DSP) or a macromolecular protein drug (bevacizumab) or both was formulated with this BioSeizer. To assess the sustained release capability of BioSeizer, in vitro and in vivo pharmacokinetic studies were done. The DSP or bevacizumab/BioSeizer were injected separately into the vitreous (IVI) of rabbits. The animals were sacrificed at each time point and the eyes enucleated for the assessment of vitreous concentration of drugs. In another experiment, to assess the effectiveness of this slow release system, a rabbit model of blood retinal barrier (BRB) breakdown was used to test the prolong effect of IVI lipid based drug with DSP.

Results: The in vivo release of DSP or bevacizumab, can be sustained in the vitreous chamber for more than four months by a single intravitreal injection of a lipid-based formulation, with a sufficient rate of drug release to maintain a vitreous concentration of drugs equivalent to that of commercial formulation. No toxic effects were found. In the efficacy study, free DSP did not have a significant effect on the blockade of BRB breakdown beyond 9 days post-administration. In contrast, the DSP/BioSeizer continued to significantly inhibit BRB breakdown 72 days after administration.

Conclusions: These findings suggest that lipid-based drug delivery system can provide long-term and therapeutic concentration of drugs in vitreous.

Keywords: 763 vitreous • 412 age-related macular degeneration • 748 vascular endothelial growth factor