Effect of sterilization by steam and pressure and gamma radiation on drug-loaded intraocular lenses for prophylaxis of endophthalmitis

Abstract

Introduction: Cataracts surgery involves the removal of the opacified natural lens and implantation of an intraocular lens (IOL). However, in the post-operatory period, complications such as endophthalmitis can appear. To prevent this, antibiotics and anti-inflammatories are administered in eye drops with a very frequent posology. This drug delivery method leads to a low bioavailability of the drugs in the eye and seldom to low patient compliance. To overcome these problems, it has been explored the possibility of using drug-loaded IOLs. Since IOLs are place inside the eye, sterilization is mandatory. Although there are some sterilization methods well-defined, some concerns are raised about their effects on drug loaded systems. In this work the effect of two common sterilization methods (steam and pressure and gamma radiation) on IOLs properties and on the drug release from drug-loaded IOLs is investigated.

Materials and methods: Acrylic IOLs with 26% of swelling capacity, an antibiotic, moxifloxacin (MXF), and two anti-inflammatories, ketorolac (KTL) and diclofenac (DFN) were used. First, it was studied the effect of sterilization on the lenses properties such as the swelling capacity, optical properties (transmittance) and mechanical properties (Young’s modulus). Then, the drugs were loaded into the IOLs by soaking (5 mg/mL) at 60 °C for 14 days and the effect of sterilization in the release of the drugs was evaluated. In vitro drug release experiments were carried out in sink conditions. Two methods of sterilization were experimented: steam and pressure by autoclaving (121 °C, 1bar, 1h) and gamma radiation (25 kGy, rate 2.5 kGy/h). For steam and pressure the lenses were sterilized hydrated in the 1st day or in the last day of loading (14th day). For gamma radiation the lenses were sterilized in dried state, due to degradation of drugs by gamma radiation when in aqueous solution. In this case, sterilization was carried out after 14 days of loading and 7 days of vacuum drying. A mathematical model was applied to predict the in vivo efficacy of the drug release profile for the best system.

Results: Regarding the effects on the lenses properties, sterilization by autoclaving slightly increased the Young’s modulus, while gamma radiation slightly increased the transmittance in the 400-500 nm region. However, the observed changes do not compromise the use of the lenses. Concerning the drug-loaded lenses, it was observed that although steam and pressure done in the 1st day of loading does not affect the release of the drugs, when done in the 14th day decreases significantly the amount of drug release for all three drugs. Gamma radiation slightly increased the released amount only for lenses loaded with MXF. The application of the mathematical model suggests that the steam and pressure sterilized lenses at 1st day comply with the therapeutic needs.

Discussion and conclusions: Sterilization by steam and pressure when done in 1st day of loading or gamma radiation after loading and drying can be used as sterilization methods, since they do not affect significantly the lenses properties or the drugs release. As the IOLs are generally used in hydrated state at the time of the surgery, steam and pressure is the ideal sterilization method for drug-loaded IOLs.

Acknowledgements

Funding from Fundação para a Ciência e Tecnologia (FCT) [projects UID/QUI/00100/2013 and PTDC/CTM-BIO/3640/2014] and support from PhysIOL for providing the IOLS materials.