Total concentrations Wnt Pathway of celecoxib significantly h Forth in the CSA group compared with the celecoxib group for all tissues of the eye posterior au RPE choro he Of and periocular tissues. The comparison of the CSA delivery of celecoxib have shown that CSA is a total of 3 delivery h times forth in the sclera, retina, Glask body and lens of celecoxib. There was no significant difference in the delivery of CSA and celecoxib in the choro Of RPE and periokul Re tissue samples.

Wnt Pathway chemical structure

The cytotoxicity t prodrug of CSA. The effect of CSA on cell growth was also examined to assess the effects of the toxic prodrugs. The toxicity Tsprofil was prepared as a function of the concentration of prodrug by a CSA standard MTT Zelllebensf Ability assay determined using the ARPE 19 cell line. In vitro studies have shown that CSA prodrug no significant toxicity T is the concentration range induce from 0.1 m to 1 mm.
Translation Discussion clinical transscleral retinal drug delivery is partly due to poor drug delivery through the barrier underlying RPE choro The sclera failed. Based on our previous studies we have found that lipophilic drugs are retained in melanin choro Of RPE pigment rich, harm their transscleral delivery to the retina. Delivery of lipophilic drugs is more limited because of its length Solubility and disabled low concentration. In this study, we developed hydrophilic, water- Soluble prodrugs ofcelecoxib and identifies a prodrug of the fa Is a dramatically lower affinity t and h for melanin Ago transscleral delivery in vitro and in vivo. In addition, the prodrug has been converted to the parent compound in RPE choro And the retina and was not cytotoxic to cells of the pigment epithelium. These results are listed below. Transscleral delivery of lipophilic drug to the retina is severely hindered by the binding of drugs to the choro Range of RPE pigment. Celecoxib delivery to the retina is much lower than SD rats due to the accumulation of pigmented rats26 celecoxib in RPE choro Pigment.
These differences are most dramatic when the drug incomplete slow-release systems, due to the Ndigen S Saturation of the pigment is administered. Previous reports have shown that the binding of drug molecules to melanin pigment of lipophilicity and gel Most charge.29, 30 In general, the lipophilic drug molecules bind is governed by positive charges and preferably reduced to melanin For pigment.27 celecoxib Pigmentbindeverm Gene we prepared hydrophilic prodrugs of celecoxib through association with vinegar anhydride, maleic anhydride, succinic anhydride or carboxamide bond as shown in Figure 1. The disappearance of the molecular ion peak at m / z 380 and appearance of the peaks of molecular ions best at m / z 422, 478.3 and 480 of the mass spectral analysis preferential formation of the three prodrug. All three prodrugs are more hydrophilic than celecoxib, au Addition, the CSA and CMA, the negative charge OOH in their structure, which further reduces their interaction with the pigment melanin. We suspect that the H2 in celecoxib group also responsible for ionic interactions and hydrogen bonds with melanin. Conjugation of this H2 fraction in Pro prodrugs m for may have inhibited these interactions and binding reduced melanin. In line with our hypothesis, showed in vitro binding studies of melanin that all.