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Lisa C. du Toit, Viness Pillay, Trevor R. Carmichael, Thirumala Govender, Yahya E. Choonara; In Vivo Verification of the Bioresponsive Potential of an Intelligent Intraocular Implant. Invest. Ophthalmol. Vis. Sci. 2012;53(14):484.
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© ARVO (1962-2015); The Authors (2016-present)
An autofeedback polymeric platform was used in the design of an intelligent intraocular implant - the I3 - using stimuli-responsive polymers, producing a smart release system capable of delivering therapeutic levels of anti-inflammatory agent and antibiotic for posterior segment disorders of the eye in response to inflammation. Here the I3 was assessed for its ability to respond to the inflammatory state created in a suitable animal model.
In vivo design and surgical technique in the healthy rabbit eye: Fifty New Zealand Albino rabbits were used, randomly assigned to the experimental (25 rabbits) and control (25 rabbits) groups (n=5). A placebo device was implanted into one eye of the control group at sub-Tenon’s space and the drug-loaded implant (containing indomethacin and ciprofloxacin) into one eye of the experimental group. All procedures were undertaken in accordance with ARVO. For each study, one animal in each group was euthanized at each sampling point (3, 7, 14, 21, 28 days) with consequent device removal, enucleation and vitreous humor aspiration. In vivo design and surgical technique in the inflamed rabbit eye: Rabbits were assigned to experimental (5 rabbits) and control (5 rabbits) groups (n=5 at the sampling point on day 7). Device implantation in the control and experimental groups was on day 0. Intraocular inflammation was induced via intravitreal injection of Salmonella typhimurium lipopolysaccharide (LPS) (100-200 ng/10μL of phosphate-buffered saline) into the I3-implanted eye of each rabbit. One animal in each group was euthanized on day 7 with device removal, enucleation and vitreous aspiration. Analysis of implant, tissue and fluid samples: Device biocompatibility and the degree of inflammation present were histologically established. The disparity in drug release behaviour in the healthy versus the inflamed rabbit eye was ascertained via analysis of vitreous samples.
Histological evaluation indicated that sub-Tenon device implantation did not induce a notable degree of inflammation. In vivo results demonstrated good penetration of drug from sub-Tenon’s space, through the ocular membranes, into the vitreous humour. There was enhanced release of both drugs in the inflamed rabbit eye even after 7 days with indomethacin levels of 0.749±0.126µg/mL and 1.168±0.186µg/mL, and ciprofloxacin levels of 1.181±0.150µg/mL and 6.653±0.605µg/mL being attained in the normal and inflamed eye, respectively.
The I3 displayed exemplary inflammation-responsive behaviour following assessment in a rabbit eye model.
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