![]() These challenges are being addressed with a wide variety of academic and industrial research efforts in exploring new delivery routes and developing improved formulations to deliver the drug to the posterior segment less invasively. Therefore, there is a tremendous need to develop new therapies and improve drug delivery methods for posterior segment diseases. So far, no clinical successes have been seen in developing oral or other less invasive treatments for these diseases. For others, such as the wet form of AMD, diabetic retinopathy and macular edema, treatments are delivered through frequent intravitreal injections. For many posterior segment diseases, such as the dry form of age-related macular degeneration (AMD) and normotensive glaucoma, there are no treatments available. Treating these diseases, however, remains challenging, due to limitations in available drugs and drug delivery methods. Overall, the developed method enables a reliable determination of small molecule drug concentrations in ocular tissues to support ocular drug research and development.ĭiseases of the posterior segment of the eye are the leading causes of blindness in many western countries. Additionally, clear differences were observed in the BN rat tissue partitioning compared to the WH rat. Kp values of individual tissues varied up to 100-fold in WH and up to 46,000-fold in BN rats highlighting the importance of measuring concentration directly from the ocular tissue of interest. The inter-individual variability in tissue partitioning coefficients (Kp) was low, demonstrating the reproducibility of the separation method. Following oral administration, we applied the tissue separation method, in order to determine the ocular concentrations of dexamethasone and levofloxacin, as well as two in-house molecules BI 113823 and BI 1026706, compounds differing in their melanin binding. A short formalin incubation, which did not interfere with drug quantification, enabled the preservation of individual tissue sections while minimizing cross-tissue contamination, as demonstrated by histological analysis. ![]() To understand the intraocular drug distribution, we developed a robust method for the separation of individual anterior and posterior substructures of pigmented Brown Norway (BN) and albino Wistar Han (WH) rat eyes, followed by quantification of drug concentration in these substructures. Detailed methods of separating rat ocular tissues have not been described in literature. The rat is a commonly used species in ocular drug research. ![]()
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