Abstract
Purpose: :
To design a low-cost intraocular implant using vicryl suture for the delivery of pharmacological agents to the posterior segment of the eye, using acetylsalicylic acid (ASA) as a model system for its potential in treating diabetic and other retinopathies.
Methods: :
Vicryl suture devices were designed as a coil of vicryl wrapped around a core consisting of 5-10 vicryl filaments. Devices were impregnated with ASA, then incubated in vitro either in water or cell culture medium. Samples for each experiment were obtained at varying time points up to 48 hours to measure drug elution rate. Visible spectrophotometry was used to quantify ASA elution in water. Levels of ASA eluted into culture medium with serum were analyzed by HPLC using ibuprofen as an internal standard. Controls consisted of devices not loaded with ASA.
Results: :
Quantification of ASA in water by visible spectrophotometry demonstrated measurable levels of ASA eluting from the vicryl suture device. Levels of ASA increased gradually and reached peak concentrations by 24 hours. The device with only 5 core filaments delivered a maximum of 94.3 ug/ml over 24 hours, while the device with 10 core filaments delivered up to 486.8 ug/ml in 24 hours. Elution of both ASA and salicylic acid (SA), the hydrolysis product of ASA, into cell culture medium was analyzed by HPLC. Levels of total estimated salicylate peaked near 24 hours, corresponding with the time to reach peak levels as measured by visible spectrophotometry. Results also showed a rapid hydrolysis of ASA to salicylic acid within 2-4 hours, as levels of ASA dropped to undetectable levels while SA concentrations increased.
Conclusions: :
Our study suggests that an intraocular implantable device fashioned from vicryl suture is capable of delivering therapeutic amounts of ASA for at least 48 hours, often with drug levels comparable to those observed in studies utilizing other methods of ASA administration. The correlation between peak levels and number of core filaments suggests that increasing the number of filaments may increase the capacity for the device to carry and deliver the drug. Using aspirin as a model provides the potential to further investigate the ability of NSAIDs to inhibit inflammation and neovascularization associated with retinopathy.
Keywords: diabetic retinopathy • drug toxicity/drug effects • neovascularization