Studies on the interactions of tissue plasminogen activator (tPA) and plasminogen with polyurethane surfaces containing epsilon-lysine moieties (epsilon-amino group free) are reported. These surfaces are considered to have the potential to dissolve nascent clots that may be formed on them. For adsorption from both single protein solutions and plasma, the surfaces were found to have a high capacity for tPA as well as plasminogen. A significant fraction of preadsorbed tPA was displaced from the epsilon-lysine surfaces upon contact with plasma. These surfaces, when preadsorbed with tPA and then incubated with plasma, were able to dissolve incipient clots formed around them. However, the clot-dissolving capacity diminished as the time of plasma incubation increased, presumably due to loss of tPA. It was also shown that in plasma, preadsorbed tPA is displaced from these surfaces largely by plasminogen, which thus appears to have a greater binding affinity than tPA for the epsilon-lysine moieties. Finally, it was found that in plasma, the epsilon-lysine surfaces interact with plasminogen in a dynamic manner, and that about 70% of the bound plasminogen is exchanging continuously with plasminogen in the plasma.

A biocompatible, sustained-release subretinal drug-delivery platform was developed to overcome the therapeutic accessibility limitations of current retinal disease treatments. The prototype implants were fabricated by coating nitinol, poly(methyl methacrylate) or chromic gut core filaments, with a drug-eluting polymer matrix. The polymer coatings are manufactured and coated by SurModics. The coating is a mixture of poly(butyl methacrylate) and poly(ethylene-co-vinyl acetate). The drug is either triamcinolone acetonide or sirolimus. The rods were successfully implanted into the subretinal space of 20/24 rabbits. Four rabbits were lost to early surgery from a dysfunctional infusion line and hemorrhage. No serious complications were observed during the 4-week follow-up period. Slight conjunctival redness was reported in all rabbits by 1-day follow-up, but the redness had subsided by the following week. Intraocular lens touch occurred in six rabbits during the implantations; of these, four had a lensectomy at the time of surgery, and the remaining two developed cataract. Corneal edema developed in three rabbits by 1-week follow-up, but subsided within 2 weeks. Initial observations of the implantation and elution characteristics revealed that the implants are well tolerated by the retinal tissue and that the implant can elute triamcinolone acetonide for a period of at least 4 weeks without eliciting an inflammatory response or complications. There were adverse clinical indications with the sirolimus-loaded implants at the delivered dose. Device retrieval required an uncomplicated surgical procedure, and revealed no associated or adherent tissue. Implant drug content analysis and opacity changes to the polymer matrix coating following retrieval demonstrated the sustained elution of the drug.

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