18-Month Intraocular Viability and Drug Delivery Kinetics of Polymer Encapsulated Cells Used in the Treatment of Retinal Disorders

Abstract

Purpose: : The goal of the Neurotech's Encapsulated Cell Technology (ECT) is to deliver therapeutic factors produced by the encapsulated cells de novo over an extended implantation period mitigating the requirements of standard delivery methods such as chronic intraocular drug injections. This study reports on the efforts to optimize implant viability of polymer encapsulated cells and increase stability of cellular drug delivery as a means to maximize the therapeutic potential of ECT in the treatment of retinal disorders.

Methods: : The ECT device design currently used in clinical trial applications was modified to optimize the viability of the encapsulated cell mass and improve drug release kinetics over the course of an extended implantation period. Human retinal pigment epithelial (hRPE) cells genetically modified to secrete human ciliary neurotrophic factor (hCNTF) were encapsulated in the modified polymer capsules and evaluated both in vitro and following intraocular implantation into rabbit vitreous over the course of 1.5 years. Encapsulated cell mass and viability was evaluated by DNA quantitation as well as by histomorphologic evaluation of H&E stained device sections. hCNTF kinetics was determined by ELISA quantitation of the vitreous hCNTF levels based on a single-compartment model with 1^st order elimination. Ocular toxicity was monitored by direct and indirect fundus examinations as well as by pathological tissue evaluations conducted throughout the course of the study. Animal serum was evaluated for antibodies to hCNTF and to the encapsulated cells.

Results: : Cell viability and cell mass remain equivalent comparing pre-implant and 1.5 year devices explanted from the rabbit vitreous. hCNTF levels produced by the cell encapsulated devices prior to implantation ranged between 10-15 ng/day and following a 1.5 year implant ranged from 4-10 ng/day. Vitreous hCNTF levels evaluated from the 1-month to the 1.5 year implant time period result in a half-life calculation of 230 days. Ocular examinations and retinal pathology revealed no signs of toxicity. No antibodies to hCNTF or the hRPE cells were detected in the animal serum.

Keywords: retina • growth factors/growth factor receptors • apoptosis/cell death