Inhibitory Effect On Allograft Rejection Of A771726 Drug Delivery System, The Active Metabolite Of Leflunomide

1. A771726 drug delivery system preparation and drug release test in vitroObjective: to prepare A771726 drug delivery system, to analyse physicochemical character, drug release test.Methods: electron microscopy scanning, degeneration rate and swelling rate analysis, daily drug release count.Result: A771726 granule mix uniformly with basement. 15d, 30d, 60d degeneration rate is respectively 20.12%,39.67%,72.35%. 48h swelling rate is 300%. Drug released steady after 2 day's impact release.Conclusion: chitosan-gelatin-A771726 drug delivery system is suited to ophthalmologic application.2. Biocompatibility analysis of A771726 drug delivery systemObjective: To observe degradation of drug delivery system under rabbit conjunctiva and in chamber, eye stimulus reaction, intraocular pressure(IOP), and pathological change. To estimate the safety of A771726 delivery system.Methods: 40 cases were divided randomly into 4 groups: Group A treated with PBS; group B with 2% A771726 eye drops; group C with implantion of GICS-A771726 sub-conjunctive; group D with implantion of GICS-A771726 in chamber. To estimate eye stimulus response, observe intraocular pressure (IOP), pathological change after operation.Results: GICS-A771726 is unirritative. There is no ocular hypertension. 4 weeks after operation, film was partially fractured and absorbed. Conclusion: GICS-A771726 has good histocompatibility.3. Inhibitory effect on corneal neovascularization of A771726 drug delivery systemObjective: To investigate the inhibitory effect on corneal neovascularization of A771726 drug delivery system.Methods: The corneal neovascularization was induced by corneal alkali burn in rabbits, then 30 rabbits were randomly divided into 3 groups. Group A treated with buffer salt solution; Group B with 2.0% A771726; Group C with A771726 drug delivery system subconjunctival implantation. The occurrence and development of corneal neovasculariza tion were observed with slit lamp microscope. Neovascularization index (NI) were recorded and compared among different groups. VEGF in corneal were detected by immunohistochemestry staining.Result: The corneal neovascularization areas in Group B and Group C were significantly smaller than that in Group A in 7,14and 28 days after corneal alkali burn(P<0.05). The immunohistochemestry staining of Group B and Group C were weakened significantly than Group A. Conclusions: A771726 inhibit coneal neovascularization by inhibit VEGF.GICS-A771726 reduce drug usage counter.4. Inhibitory effect on allograft rejection of A771726 drug delivery systemObjective: To investigate the inhibitory effect on allograft rejection of A771726 drug delivery system.Methods: 30 rabbits with corneal neovascularization were randomly divided into 3 groups and treat with transplatatin. Group A treated with buffer salt solution; Group B with 2.0% A771726; Group C with A771726 drug delivery system implantation in the chamber. Rejection Index (RI) were counted with slit lamp microscope. VEGF and TNF-αin corneal were detected by immunohistochemestry staining. A HPLC method was developed to determine the chamber level of A771726.Result: averagy survival time are 17.80±4.18d in Group A, >26.70±2.83d in Group B,>26.50±2.72d in Group C。The immunohistochemestry staining of Group B and Group C were weakened significantly than Group A. Everagy drug concentration in Group A on 7,14,21,28d are 15.20±1.81,18.00±3.33,14.00±2.40,10.00±1.49ng/ml。Conclusions: A771726 inhibit coneal allograft rejection by inhibit VEGF, TNF-α. GICS-A771726 reduce drug usage counter.