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W. Tente, P. O'Rourke, S. Sherman, K. Kauper, C. McGovern, S. Matteus, B. Dean, W. Tao, C. Thanos; Sustained Delivery of hCNTF to Rabbit Vitreous Humor by Two Polymer Encapsulated Cell Lines in the NT–502 Device . Invest. Ophthalmol. Vis. Sci. 2004;45(13):5049.
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Purpose: We have evaluated and reported previously on the pharmacology and efficacy of the NT–501 1.1 cm–long device in rabbit eyes. The objective of the current study is to evaluate the pharmacokinetics, wound healing response, and the effect of pre–implant hold duration of a 6 mm device (NT–502) following implantation into the vitreous of rabbits. This study compares two encapsulated cell lines with different rates of hCNTF production based both on vitreal hCNTF concentration as well as post–explant device output up to 180 days. Methods: Polymer capsules were loaded with either NTC–201–10 (low producer) or NTC–201–6A cells (high producer). Devices were held in closed containers with 40 mL Endothelial Serum–Free Media (ENDO–SFM) for either 4 or 8 weeks prior to implantation and were surgically inserted into the vitreous of each eye of New Zealand White rabbits at the level of the pars plana. Explant of the device and collection of the vitreous occurred at 2, 4, 12, and 24 weeks following implantation (n=6 eyes at each time point). Vitreal hCNTF concentration and explanted device hCNTF production were quantified using a commercially available ELISA. Results: Devices held in vitro for 4 or 8 weeks secreted statistically similar levels of CNTF immediately prior to implantation (NTC–201–10: 7.9 ± 4.5 ng/device/24 hours [4 wks.] and 6.2 ± 1.9 ng /device/24 hours [8 wks.]; NTC–201–6A: 19.8 ± 10.6 ng/dev/24 hours [4 wks.] and 24.7 ± 10.7 ng/dev/24 hours [8 wks.]). A consistent level of hCNTF was detected in vitreal samples that received either encapsulated NTC–201–10 or NTC–201–6A cell implants. Zero–order pharmacology was observed for the duration of the study with NT–502–6A based on explanted device output as well as recovered vitreous. Both cell lines produced equivalent levels of CNTF in vitro and in vivo independent of pre–implant hold duration. Throughout the study, no significant adverse events were noted. Conclusions:The NT–502 device configuration offers a reduction in CNTF dose compared to the standard length NT–501 device and is capable of sustained secretion to the rabbit vitreous. Additionally, the wound healing response is extremely minimal with even reduced potential for inflammation of the lens due to proximity.
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