5-FU loaded pHEMA drainage implants for glaucoma-filtering surgery: device design and in vitro release kinetics.

Implantable monolithic and reservoir-like water-swellable drainage devices were developed for the subconjunctival sustained release of 5-fluorouracil (5-FU) in glaucoma-filtering surgery. A water-swellable matrix was formed of a copolymer of 2-hydroxyethyl methacrylate (HEMA) with different amounts of ethylene glycol dimethacrylate (EGDMA). Drug incorporation was done before polymerization and cross-linking. Briefly, to prepare the monolithic device the monomer-drug mixture is compression moulded into a 10 mm cylinder of 1 mm length. Furthermore, reservoir-like devices were obtained by coating the monolithic devices with a highly cross-linked polymer of HEMA (pHEMA) composition. The pHEMA devices containing 5-FU or not were well characterized by means of dynamic swelling studies, structural and thermal analysis. The release of 5-FU from these implants was studied in vitro. The rate of drug release was controlled by changing the drug loading (i.e. 10 mg or 20 mg 5-FU per device), cross-linking density of polymer matrix and type of implantable device, i.e. monolithic or reservoir-like device. While monolithic devices are releasing total releasable 5-FU during the first 10 h, reservoir-like devices prolong 5-FU release for up to 120 h. The 5-FU diffusion coefficient in swollen devices (Ds,s) is in the order of 10(-8) cm2 s-1 (approximately 10 times smaller than Dw,g values) and it is dependent on the cross-linking density of polymeric matrix and device load. These preliminary results suggested that 20 mg 5-FU-loaded reservoir-like devices may be a potentially effective system to deliver 5-FU into the subconjunctiva.

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.

Antioxidative role of ocular melanin pigment in the model of lens induced uveitis.

Ocular melanin pigment has antioxidant effect against excess of dispersed light. To investigate whether it has a similar effect in ocular inflammations, we used albino and pigmented guinea pigs and measured retinal glutathione peroxidase activities and lipid peroxide levels (expressed as thiobarbituric acid reactive substances) in a model of lens induced uveitis. Although the increase in the levels of the retinal lipid peroxides were higher in the albino group (204%, p < 0.05), the decrease in the activities of glutathione peroxidase were higher in pigmented guinea pigs (26%, p < 0.005). The results of the study suggest that pigmentless animals are more sensitive to the ocular inflammations, and ocular melanin pigment may act as an endojen antioxidant in lens induced uveitis.

Mononuclear cell phenotypes and immunoglobulin gene rearrangements in lacrimal gland biopsies from patients with Sjögren's syndrome.

Immunocytochemical studies of lacrimal gland biopsies obtained from eight patients with Sjögren's syndrome revealed the major component of the mononuclear cell infiltrates to be comprised of B cells and Leu-3+ T-helper cells, which were present well in excess of control glands. Three of seven cases that were tested harbored cells that stained with monoclonal antibodies against different components of Epstein-Barr virus (EBV); one of the biopsies also contained cells that bore cytomegalovirus antigens. Immunoglobulin-gene rearrangements, but not T-cell receptor rearrangements, were demonstrated in one of two Sjögren's lacrimal gland biopsies tested. The authors conclude that the destruction of the tubuloacinar architecture of lacrimal gland tissue in Sjögren's syndrome appears secondary to lymphoproliferation of B cells and T-helper cells, probably derived from primary lymphoid follicles. Productive infection of lacrimal gland tissue with EBV may play a role in the pathogenesis of the syndrome in selective cases.