Supercritical fluid technology for the development of innovative ophthalmic medical devices: Drug loaded intraocular lenses to mitigate posterior capsule opacification

Supercritical impregnation technology was applied to load acrylic intraocular lenses (IOLs) with methotrexate to produce a sustained drug delivery device to mitigate posterior capsule opacification. Drug release kinetics were studied in vitro and used to determine the drug loading. Loaded IOLs and control IOLs treated under the same operating conditions, but without drug, were implanted ex vivo in human donor capsular bags. The typical cell growth was observed and immunofluorescence staining of three common fibrosis markers, fibronectin, F-actin and alpha-smooth muscle actin was carried out. Transparent IOLs presenting a sustained release of methotrexate for more than 80 days were produced. Drug loading varying between 0.43 and 0.75 +/- 0.03 mu g(dru)(g).mg(IOL)(-1) were obtained when varying the supercritical impregnation pressure (8 and 25 MPa) and duration (30 and 240 min) at 308 K. The use of ethanol (5 mol%) as a co-solvent did not influence the impregnation efficiency and was even unfavorable at certain conditions. Even if the implantation of methotrexate loaded IOLs did not lead to a statistically significant variation in the duration required for a full cell coverage of the posterior capsule in the human capsular bag model, it was shown to reduce fibrosis by inhibiting epithelial-mesenchymal transformation. The innovative application presented has the potential to gain clinical relevance.