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Berenice Coquerel, Etienne Gardea, Denis Gruber, Raymond Andrieu, Della Martina Alberto, Marc Muraine; In Vitro Assays On Polydioxanone Membranes Use As Mitomycin C Delivery System For Glaucoma Treatment. Invest. Ophthalmol. Vis. Sci. 2011;52(14):466.
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The aim of this study was to investigate the release kinetic of Mitomycin C (MMC) delivered onto polydioxanone (PDO) membrane using analytical chemistry and to evaluate this cellular effect to control and quantify its ability to avoid human ocular fibroblast to proliferate. Indeed, the development of an effective long lasting drug delivery system after glaucoma surgery could minimize side effects and increase patient compliance.
PDS membranes, including or not MMC, were immersed in fresh saline to determine release kinetics. After many developments to optimize the analytical conditions of the quantification of the delivered MMC, analysis was performed by high-pressure liquid chromatography (HPLC). HPLC column retention time was determined for drug released compared to a standard curve to determine the exact amount of released MMC. In a second time, the supernatant was added to a primary ocular fibroblast cell culture to determine the efficiency of the MMC delivered by the system and the inhibition proliferation rate. Then membranes, containing or not MMC, were added directly on the cell layer or placed in a transwell device and the inhibition proliferation rate was also determinate for 10-5 g of MMC.
The kinetic of the MMC release by the PDO membrane has been determined. A perfect correlation between the size of the membrane including MMC and the amount of MMC delivery has been observed, each mm2 delivers 7.10-7 g of MMC and the retention time is 4.1 minutes. In three days the whole amount of MMC has been delivered by the membrane. Using MMC-PDO membrane supernatant or MMC-PDS membrane placed in transwell device, the inhibition of the proliferation was respectively 95.4 % and 91.1 % (p< 0.001) with no statistical difference between the 2 techniques.
With the help of the MMC-PDO we have quantify the long time drug delivery in an in vitro model. MMC delivered by this system is efficient on human primary ocular fibroblasts and could statistically inhibit the cellular proliferation. Further tests on rabbit glaucoma model have highlighted no local inflammatory reaction with the polydioxanone membrane and less scar tissue formation with MMC-PDO membrane.
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