Delivery of a novel neuroprotective compound to the retina in rat and rabbit animal models

Posterior segment-related diseases are among the leading causes of irreversible blindness and loss of vision globally. These diseases are extremely difficult to treat due to the drug delivery barriers posed by the eye, among other challenges. One delivery method that bypasses many of these obstacles, albeit not without risk, is ocular injections, and long-acting formulations such as implants can improve patient compliance by allowing for longer intervals between injections. Here, we report our development of a preclinical in situ-forming implant dosage form that provides sustained release of a novel compound, DKR-1677, with a target in the retina. An in situ-forming implant based on polylactic co glycolic acid (PLGA) was chosen in this preclinical stage because it is readily translatable to a preformed implant product. The formulations were tested in vitro, in rat and rabbit animal models for drug release and pharmacokinetics. A two-step in vitro dissolution method with implant formation in a biorelevant gel followed by incubation in release media showed a 30-day three-phase release profile with an initial burst release of 36.04 ± 4.23 %, a plateau, and a controlled release up to 93.75 ± 4.68 % at day 30, typical of PLGA-based implant formulations. Immediate and controlled-release formulations were tested in rat and rabbit animal models and confirmed that DKR-1677 is taken up by the retina after intravitreal administration. Furthermore, the in situ-forming implant was found to prolong drug presence in the retina to 30 days following a single administration, confirming that a PLGA-based implant is a viable approach for this drug candidate.