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CG Thanos, WJ Bell, P O'Rourke, V Budz, S Sherman, K Kauper, B Dean, P Stabila, M Goddard, W Tao; Sustained Delivery of hCNTF to Rabbit Vitreous Humor by Two Polymer Encapsulated Cell Lines . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2314.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The objective of this study is to evaluate the pharmacokinetics of hCNTF in the vitreous humor when delivered via polymer encapsulated cells implanted in the vitreous of rabbit eyes. 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 90 days. Methods: Polymer capsules were loaded with either NTC-201-10 (low producer) or NTC-201-6A cells (high producer). A cell-loaded capsule was surgically implanted into the vitreous of each eye in New Zealand White rabbits. One group received capsules containing NTC-201-10, the other NTC-201-6A cells. Explant of the capsule and collection of the vitreous occurred at 1, 3, 7, 14, 30, 60 and 90 days following implantation (n=10 eyes at each time point, n=4 eyes at 60 days). Vitreal hCNTF concentration and explanted capsule hCNTF production were quantified using a commercially produced ELISA. Results: A consistent level of hCNTF was detected in vitreal samples that received either encapsulated NTC-201-10 or NTC-201-6A cell implants. A distinct steady state was achieved for each cell line after approximately 2 weeks following implantation. For the NTC-201-10 cell line, the hCNTF production of the explanted capsules was 1∼5 ng/day with vitreal hCNTF at 50∼200 pg/ml. For the NTC-201-6A cell line, the CNTF production of the explanted capsule was 10∼20 ng/day with vitreal hCNTF at 0.5∼1.5 ng/ml. hCNTF was not detected in baseline samples of rabbit vitreous (LOQ = 30 pg/mL). The recovery of hCNTF from the vitreal samples is approximately 50% based on spike/recovery samples. Conclusion: Implantation of cell-loaded capsules into the vitreous of the rabbit eye resulted in a sustained delivery of hCNTF to the vitreous humor. This study shows that hCNTF, in measurable concentrations, is deliverable to the rabbit vitreous humor, and the vitreal concentration may be dependent on the production rate of the cell lines. These results suggest that encapsulated cell based delivery may have important applications for the treatment of ophthalmic diseases where continuous local delivery of therapeutic factors is indicated.
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