OBJECTIVE: To determine the efficacy and pharmacokinetics of an intravitreal sustained-release triamcinolone acetonide and 5-fluorouracil (TA/5-FU) codrug in the treatment of experimental proliferative vitreoretinopathy (PVR). METHODS: The therapeutic efficacy of the TA/5-FU codrug was determined in a rabbit model that simulates human PVR. Intravitreal levels of triamcinolone and 5-fluorouracil were measured at different time points and drug release in vitro was tested. Toxic effects were evaluatedby electroretinograpy, clinical examination, and light microscopy. RESULTS: Both the severity of PVR grade and the percentage of eyes with moderate or worse tractional detachment were significantly less in eyes treated with the codrug. The therapeutic effect of the intravitreal codrug was paralleled by sustained intravitreal levels of triamcinolone and 5-fluorouracil. There were no drug-related toxic effects evident on clinical or histopathologic examination of eyes containing the TA/5-FU codrug. CONCLUSIONS: The intravitreal sustained-release TA/5-FU codrug effectively inhibits the progression of PVR in a rabbit model that closely resembles PVR in humans. The TA/5-FU codrug may simultaneously target different components of the wound-healing response.
OBJECTIVE: To determine the efficacy and pharmacokinetics of an intravitreal sustained-release triamcinolone acetonide and 5-fluorouracil (TA/5-FU) codrug in the treatment of experimental proliferative vitreoretinopathy (PVR). METHODS: The therapeutic efficacy of the TA/5-FU codrug was determined in a rabbit model that simulates human PVR. Intravitreal levels of triamcinolone and 5-fluorouracil were measured at different time points and drug release in vitro was tested. Toxic effects were evaluatedby electroretinograpy, clinical examination, and light microscopy. RESULTS: Both the severity of PVR grade and the percentage of eyes with moderate or worse tractional detachment were significantly less in eyes treated with the codrug. The therapeutic effect of the intravitreal codrug was paralleled by sustained intravitreal levels of triamcinolone and 5-fluorouracil. There were no drug-related toxic effects evident on clinical or histopathologic examination of eyes containing the TA/5-FU codrug. CONCLUSIONS: The intravitreal sustained-release TA/5-FU codrug effectively inhibits the progression of PVR in a rabbit model that closely resembles PVR in humans. The TA/5-FU codrug may simultaneously target different components of the wound-healing response.
Authors: Flávia Carmo Horta Pinto; Armando Da Silva-Cunha Junior; Rodrigo Lambert Oréfice; Eliane Ayres; Silvia Passos Andrade; Luiza Dias C Lima; Sandra A Lima Moura; Gisele Rodrigues Da Silva Journal: J Mater Sci Mater Med Date: 2012-04-01 Impact factor: 3.896
Authors: J A Cardillo; M E Farah; J Mitre; P H Morales; R A Costa; L A S Melo; B Kuppermann; R Jorge; P Ashton Journal: Br J Ophthalmol Date: 2004-09 Impact factor: 4.638