Supercritical loading of gatifloxacin into hydrophobic foldable intraocular lenses - Process control and optimization by following in situ CO2 sorption and polymer swelling.

The supercritical impregnation process was used as a green technology for the elaboration of drug delivery intraocular lenses to mitigate the risk of post-operatory endophthalmitis after cataract surgery. Commercially available hydrophobic acrylic (copolymer of benzyl methacrylate and methyl methacrylate) intraocular lenses (IOLs) were impregnated with gatifloxacin, a fourth generation fluoroquinolone drug, using pure supercritical CO2 (scCO2) to obtain solvent-free loaded implants. The interaction phenomena involved in the supercritical impregnation were studied by following in situ scCO2 sorption within the polymer support and the subsequent IOL swelling, and by taking into account drug solubility in the supercritical fluid phase. The drug impregnation yields determined though in-vitro release studies varied between 0.33 and 1.07 ± 0.07 µg·mg-1IOL in the studied experimental conditions (8 to 25 MPa, 308 to 328 K and 30 to 240 min impregnation duration). An impregnation duration longer or equal to the time required for a complete CO2 uptake by the polymer as well as a higher pressure or a higher temperature over the crossover pressure delimiting the upper limit of the retrograde solubility zone, led to higher drug impregnation yields.

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 α-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 µgdrug·mg-1IOL 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.