Synthesis of sulfonylurea conjugated copolymer via PEO spacer and its in vitro short-term bioactivity in insulin secretion from islets of Langerhans

Biological and Biomaterial Approaches for Improved Islet Transplantation

“…Other critical requirements to the success of this technology include solubility in the cell culture medium and the physiologic milieu, as well as bioactivity of the encapsulated conjugate. Coencapsulation of this conjugate increased glucose-stimulated insulin secretion from the islets (Hwang et al, 1998), as well as from an insulinoma cell line, MIN6 (Park et al, 2001). However, the increase was seen only at basal and not at elevated glucose concentrations .…”

“…A logical approach in this direction is the use of oral hypoglycemic agents that act on the islets to enhance insulin secretory activity in type II hyperglycemic patients, e.g., the sulfonylurea drugs. Thus, Hwang et al (1998) synthesized poly(N-vinyl-2-pyrrolidone)-cosulfonylurea succinyl poly(ethylene oxide), which is a copolymer of glyburide and PVP, in which sulfonyl urea is attached to PVP via the poly(ethylene oxide) linker. Preparation of a polymeric conjugate of the active drug is necessary to increase its size into the colloidal range so that it does not diffuse out after transplantation.…”

Prolonged Glucose Normalization of Streptozotocin-Induced Diabetic Mice by Transplantation of Rat Islets Coencapsulated with Crosslinked Hemoglobin

“…For example, to enhance insulin secretion, hypoglycemic drugs, insulinotropic agents, and their polymeric derivatives, such as sulfonylurea-bound polymers and zinc-crystallized glucagons-like peptide-1, have been introduced into islet culture or islet capsules (20,21). In regard to improved oxygen supply, the uses of free Hb (22), perfluorocarbon emulsion (23), and water electrohydrolysis (24) have been attempted, resulting in enhanced islet or cell viability and functionality.…”

Islet Transplantation and Encapsulation: An Update on Recent Developments

“…This can be achieved by treating the islets with oral hypoglycemic agents such as sulfonylureas. Capitalizing on this, Hwang et al and Park et al prepared a polymeric conjugate of sulfonylureas and demonstrated increased insulin secretion by coencapsulating the conjugate with islets and insulin-producing cell lines respectively [97,98]. However, the increased insulin secretion was seen only at basal levels and did not increase with elevated glucose concentrations.…”