Dual release of an antibiotic and anti-inflammatory from intraocular lenses for prophylaxis of endophthalmitis

Abstract

Introduction: Cataract is the leading cause of blindness and affects more than 20 million people worldwide each year. It is treated by replacing the opacified crystalline lens with an implantable synthetic lens. Although considered as a very safe procedure, cataract removal surgery has associated risks of post-surgical complications, such as endophthalmitis, a serious intraocular inflammatory disorder resulting from bacterial infection. Thus, in the post-operatory period, antibiotics and anti-inflammatories eye drops are administered with a frequent posology to prevent eventual complications. This drug delivery method is not very effective and may lead to low patient compliance. In this work, it is explored the possibility of using drug-loaded IOLs to ensure a simultaneous release of both antibiotic and anti-inflammatory drugs.

Materials and methods: An antibiotic, moxifloxacin (MXF), and two anti-inflammatories, ketorolac (KTL) and diclofenac (DFN) were loaded in acrylic IOLs by soaking in drugs solutions at 60 °C for 2 weeks. The lenses were loaded in a double drug solution of MXF + KTL with a concentration of 5 mg/mL each drug and in MXF + DFN with a concentration of 1.11 mg/mL for MXF and 0.56 mg/mL for DFN due to drugs solubility constrains. Single load of the drugs (with the same concentrations) was also carried out for comparison purposes. Both double loaded lenses were sterilized by autoclaving (121 °C, 1bar, 1h). In vitro drug release experiments were performed in sink conditions. The effect of the drug loading and of the sterilization on lenses properties such as the swelling capacity, optical properties (transmittance) and mechanical properties (Young’s modulus) were evaluated. A mathematical model was applied to predict the in vivo efficacy of the drug release profile.

Results: It was observed that the double loaded lenses released a significant higher amount of each drug than the single loaded lenses, with the exception of DFN, which release remains the same when double or single loaded. The devices should be able to release effective amounts of each drug for 2-4 weeks. Sterilization by autoclaving almost did not affect the drug release profile of the double loaded lenses. It was found that the presence of drugs increases the swelling capacity of the lenses: the lenses soaked in MXF + KTL swelled more 50% than the lenses hydrated in saline solution, while in MXF + DFN swelled more 15%, independently of being sterilized or not. Concerning the optical and mechanical properties, the changes observed do not compromise the use of the lenses.

Discussion and conclusions: The sterilized and double loaded lenses comply with both antibiotic and anti-inflammatory therapeutic needs for the prophylaxis of endophthalmitis after cataract surgery, keeping adequate optical and mechanical characteristics. They may be considered a promising alternative to the commonly used drug administration route in the post-operatory period.

Acknowledgements

The authors acknowledge 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 materials for IOLs.