Purchase this article with an account.
N. Miladore, H. Nakamura, W. Geldenhuys, D. Bhatia, V. Sutariya; Thermoreversible Gel for Delivery of Activin Receptor-Like Kinase 5 Inhibitor in Glaucoma Filtration Surgery. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4444.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
It was demonstrated that activin receptor-like kinase 5 (ALK-5) inhibitors are effective in suppressing expression of downstream, scarring-related proteins of transforming growth factor-β in cultured rabbit subconjunctival fibroblasts. The purpose of this study is to develop thermoreversible gel system, which will be used for sustained drug delivery, to deliver ALK-5 inhibitor in glaucoma filtration surgery (GFS) and to investigate its efficacy and toxicity using a rabbit in vivo model.
Thermoreversible gel of Pluronic® F 127 containing SB 505124 was developed after dissolving three different concentrations of Pluronic® F 127 in the water (18, 20, 22 w/v%) at 4 °C. The mixture was stirred for 1 hour and kept at 4 °C overnight to dissolve the polymer completely. The visual observation and test tube inversion test were used to study if gel is formed at body temperature. The viscosity of the gel solution was measured using Brookfield Viscometer at different temperature and gelation temperature was identified. Their cytotoxicity was examined by MTT assay with cultured rabbit subconjunctival fibroblasts. In an in vivo rabbit GFS model, Pluronic® F 127 gel (22% w/v) of SB-505124 was delivered during the surgery. Eyes were examined by slit-lamp until the time of bleb failure after surgery.
Pluronic® F 127 gel (22 w/v%) showed a change in viscosity (from 1,000 cps to 50,000 cps) from low temperature (10°C) to body temperature (37°C) and the viscosity was stable at body temperature. The visual observation and test tube inversion test showed that the 22 % w/v Pluronic® F 127 solution showed complete gel formation at 37ºC (body temperature). MTT assay revealed that the gel is not cytotoxic to cultured cell. Filtering blebs after GFS with gel including SB-505124 (n=3) were maintained better than control (n=3). Severe post surgical complications were not observed.
Thermoreversible gel system for ALK-5 delivery was successfully developed, and the system was efficacious and non-toxic. The thermoreversible gel system may provide a novel controlled delivery system to eye including GFS.
This PDF is available to Subscribers Only