An ideal therapy should maintain effective levels of drug for the intended duration of treatment following a single application, yet a significant number of months of therapy may be required. There are numerous approaches under investigation to improve treatment options. From the use of novel biomaterial implants and depots for sustained release, to prodrug formations, to iontophoresis to improve drug delivery, the main emphasis will continue to be placed on less invasive, longer acting, sustained release formulations in the treatment of numerous ocular disorders.

Controlled, extended, and bioactive release for approximately 200 days was achieved for both ranibizumab and aflibercept in vitro. The use of anti-VEGF-loaded microspheres suspended within an injectable, thermo-responsive hydrogel may be an advantageous ocular DDS with the potential to improve upon current therapies.

In extended ocular drug delivery applications, it is necessary to exert control over the release characteristics of the drug. Design considerations must be made to limit the initial burst (IB) and ensure complete release of drug from the drug delivery system (DDS). In this study, ovalbumin was used as a model protein to explore the effects on release of polymer formulation and fabrication technique in poly(lactic-co-glycolic acid) (PLGA) microspheres. Furthermore, the effect on release of suspending these microspheres in an injectable, thermo-responsive poly(N-isopropylacrylamide)-based hydrogel was determined. To characterize release, ovalbumin was radiolabeled with iodine-125. Regardless of polymer formulation or fabrication technique, pulsatile release was achieved with a second burst occurring after ~70 days for microspheres alone. Suspending PLGA 75:25 microspheres within hydrogel reduced the IB by ~75%, delayed the second burst by 28 days, and extended release out to ~200 days with steadier, consistent release throughout compared to microspheres alone. The combined microsphere-hydrogel DDS remains injectable through small-gauge needles and may have many applications, namely ocular drug delivery to the posterior segment.

The current study demonstrates that the DDS can effectively decrease laser-induced CNV lesions in a murine model. Controlled and extended release from our DDS achieved greater treatment efficacy using an order of magnitude less drug than what is required with bolus administration. This suggests that our DDS may provide a significant advantage in the treatment of posterior segment eye diseases.

No abstract