| Cyclosporine A is a selective immunosuppressant of neutral cyclohendecapeptide separated from fungal fermentation. Since clinical application started in 1978, this agent is now widely used in homotransplantations and immunotherapy.Uveitis probably causes damages to uvea, retina and vitreous body, and it is mostly related to immunological factors. Evidence acquired from experimental and clinical researches has indicated that Cyclosporine A can affect uveitis positively.Rabbit model of panuveitis is established by subcutaneous immunization and intravitreal injection successively with 10mg and 25μg Mycobacterium Tuberculosis H37Ra antigen respectively. Rechallenge with the same amount of antigen is performed intravitreally to those rabbits to simulate the recurrence of uveitis. As reference method, the traditional method of HPLC which is already widely used in therapeutic drug monitoring has the LOQ of 50ng/ml from 2ml whole blood. Thus it can not be used for measurement of small-volume samples with low concentration of CsA. Many procedures are optimized to enhance the detection sensitivity with good results which canmeet the requirement of current research. Cyclosporine A Drug Delivery System (CsA DDS) which is carried by biodegradable PGLC is implanted intravitreally in models and vitreous samples are extracted weekly for 3 months , biweekly for another 3 months and once for another two months. The concentration of CsA is measured and the concentration-time curve is drawn, which are analyzed and evaluated.In this paper, biodegradable CsA DDS is implanted intravitreal1y on rabbit model uveitis established with Mycobacterium Tuberculosis H37Ra as antigen, intravitreal concentration of CsA is measured by a more sensitive HPLC method, and the pharmacoki net i c features of CsA DDS areevaluated. |
PDF Full Text Request