A novel MMC-loaded pHEMA drainage device for the treatment of glaucoma: in vitro and in vivo studies.
Administration of subconjunctival 5-fluorouracil (5-FU) and topical mitomycin-C (MMC) has been shown to improve the success rate of glaucoma-filtering surgery. However, corneal toxicity and administrative problems remain. To overcome this limitation, drainage devices for the sustained release of 5-FU and MMC were designed and tested in vitro and in vivo. This paper presents only the results of our studies which were carried out on MMC-loaded devices. Here, the drainage devices were prepared from MMC-loaded poly(hydroxyethyl methacrylate) (pHEMA) matrices in different cross-linking ratios and in different drug loading capacities, i.e. 0.2, 0.5, and 2.0 mg MMC per device. These devices released MMC at approximately 6.0-90.0 micrograms day-1 for over 2 months depending on cross-linking density and initial drug loading. The diffusional release of MMC from glassy and swollen copolymers showed that diffusion mechanism is Fickian in both cases. The usability of the pHEMA implants were investigated by in vivo experiments which were done on eight dog's eye. In the treatment eyes, intraocular pressures remained significantly lower than the control eyes throughout the experimental period (4 months). Subconjunctival implantations revealed no clinical and histological evidence for toxicity. The results of in vitro and in vivo studies indicate that an implantable release system delivering MMC for over 2 months can improve the prognosis for filtering surgery by preventing postoperative fibrosis.
Kiremitçi-Gümüşderelioglu
M
M
Hacettepe University, Chemical Engineering Department, Ankara, Turkey.
Gökçe
M
M
Akata
R F
RF
D000287:Administration, Topical; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D003228:Conjunctiva / Q000187:drug effects; D003315:Cornea / Q000187:drug effects / Q000473:pathology; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004285:Dogs; D016503:Drug Delivery Systems; D005355:Fibrosis / Q000517:prevention & control; D005472:Fluorouracil / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D005901:Glaucoma / Q000601:surgery*; D016685:Mitomycin / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D011102:Polyhydroxyethyl Methacrylate / Q000737:chemistry / Q000378:metabolism; D011183:Postoperative Complications / Q000517:prevention & control*; D013194:Staining and Labeling; D016707:Tissue Fixation
D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D011102:Polyhydroxyethyl Methacrylate; D016685:Mitomycin; D005472:Fluorouracil