Garret D. Figuly

Polysaccharide-Based Tissue Adhesives for Sealing Corneal Incisions

Purpose: To investigate the ability of a novel polysaccharide-based tissue adhesive to seal corneal incisions, and to determine the effect of the tissue adhesive on corneal endothelial cells. Methods: A polysaccharide-based tissue adhesive composed of dextran aldehyde and star PEG amines was applied to a 5-mm corneal incision on an enucleated rabbit eye, and the leak pressure of the eye was measured. The tissue adhesive was additionally incubated in direct contact with bovine corneal endothelial cells to evaluate cytotoxicity. Results: The polysaccharide-based tissue adhesive was successful in sealing corneal incisions to pressures of > 10 psi (500 mmHg). The tissue adhesive was non-cytotoxic to bovine corneal endothelial cells. Conclusions: Polysaccharide-based tissue adhesives are efficacious in sealing corneal wounds and are non-cytotoxic to corneal endothelial cells. Such adhesives represent a promising new technology for ophthalmic surgery.

DMP 504, a novel hydrogel bile acid sequestrant: II. Lipid‐lowering pharmacology in the hamster

DMP 504 is a novel hydrogel bile acid sequestrant in development for the treatment of moderate hypercholesterolemia. The drug is a condensation polymer synthesized from 1,10‐dibromodecane and 1,6‐diaminohexane. In vitro binding studies demonstrate that DMP 504 is superior to cholestyramine (CS) with respect to equilibrium binding capacity and affinity for bile acids. The goals of the research reported herein were to assess the in vivo hypolipidemic activity of DMP 504, to elucidate the mechanism of action of DMP 504, and to determine the potency of DMP 504 relative to CS in hamsters. Six dose groups each of DMP 504 and CS were included in the study, along with an untreated control group. The DMP 504 doses ranged from 20–1,000 mg/kg/day for 14 days; CS doses ranged from 50–2,000 mg/kg/day for 14 days. There were 48 animals per dose group; drugs were administered in the feed. At the midpoints of the dose‐response curves, DMP 504 was superior to CS with respect to increasing the output of fecal bile acids (7‐fold) and sterols (3‐fold), increasing the activity of hepatic cholesterol 7α‐hydroxylase activity (C7αOH) (6‐fold), and decreasing the circulating levels of total serum cholesterol (6‐fold), non‐HDL cholesterol (6‐fold), and HDL cholesterol (4‐fold). Neither DMP 504 nor CS had significant effects on serum triglycerides or apo‐B. In summary, DMP 504 is a new bile acid sequestrant that is mechanistically similar to CS, but is, on average, 6‐fold more potent. Drug Dev. Res. 41:65–75, 1997.