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

Abstract

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 CO 2 (scCO 2 ) to obtain solvent-free loaded implants. The interaction phenomena involved in the supercritical impregnation were studied by following in situ scCO 2 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 −1 IOL 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 CO 2 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.

Structural Modification of Polymers Functionalized with Mango Leaf Extract by Supercritical Impregnation: Approaching of Further Food and Biomedical Applications

“…These conditions favor cell growth and reduces the rejection of biomedical implants. However, in some particular cases, such as intraocular lenses [21] or in the case of stents [22], an excessive porosity of the polymer would have a negative impact on its functionality. Thus, an increment of the polymer's porosity would be associated to a higher turbidity of the material, or an excessive cell proliferation that could lead to restenosis.…”

A novel gatifloxacin-loaded intraocular lens for prophylaxis of postoperative endophthalmitis

“…However, the data of loading dose and release behavior about GAT-loaded IOLs in reported approaches was improvable. The optimized impregnation yield of GAT in IOL via CO 2 supercritical impregnation process was 1.03 ± 0.07 μg/mg, only 24.0 ± 1.2 μg GAT was released in several weeks [ 56 ]. As reported of the solution presoaking method, though more than 70 μg GAT was released in the first 24 h, only 1.9 ± 0.8 μg/mL of GAT in aqueous humors was measured 2 h after in vivo implantation, which did not reach the MIC 90 of S. epidermidis [ 27 ].…”

Therapeutic Ophthalmic Lenses: A Review

“…Supercritical fluids are characterized by a high density, low viscosity, high diffusivity, and low interfacial tension [92]. These features are favorable for the diffusion of such fluids in the polymer matrices of CLs or IOLs [26,60,[92][93][94][95][96][97]. Impregnation with a supercritical fluid consists in the dissolution of the drug in the solvent (generally supercritical CO 2 ), followed by the interaction with the target material [22].…”

“…No effect on the dioptric power of the impregnated lenses was detected [95]. Ongkasin et al recently adopted the same technique for the loading of gatifloxacin [96] into commercially available hydrophobic IOLs. The effect of the parameter optimization on the impregnation yield was evaluated, but no data on the drug release profile were reported.…”