Insulin diffusion through polymer membranes: a self-regulating isulin delivery system.

Prevention of insulin self-association and surface adsorption onto various polymeric surfaces was investigated. It was found that the addition of a certain concentration range of urea (1-3 mg/ml) to insulin solutions greatly reduces insulin self-association. The aggregation phenomena of the synthesized glycosylated insulin which will be used for a self-regulating insulin delivery system was studied. The results of the aggregation tests demonstrated glycosylated insulins to be more stable against aggregation than native insulin. This would lengthen the storage life. In order to obtain suitable polymer membranes for self-regulating insulin delivery systems, the diffusivity of sodium acetate, glucose, maltose, insulin, cytochrome C and albumin through porous and dense cellulose acetate, porous and dense regenerated cellulose, porous and dense polylactic/glycolic acid, poly-hydroxyethylmethacrylate (p-HEMA), copoly-HEMA/methoxyethylmethacrylate (MEMA), copoly-HEMA/methoxyethoxy-ethylmethacrylate (MEEMA) and porous poly-HEMA was studied. Porous polylactic/glycolic acid and porous poly-HEMA had sufficient diffusivities for both glucose and insulin. The diffusion of p-(succinylamido)-phenyl-(alpha)-D-glucopyranoside (SAPG)-Insulin and p-(succinylamido)-phenyl-(alpha)-D-mannopyranoside (SAPM)-Insulin released from their concanavalin A complexes through porous regenerated cellulose, porous polylactic/glycolic acid and porous poly-HEMA were studied. The results demonstrate that glycosylated insulin-concanavalin A complexes release their glycosylated insulins, depending on glucose concentration present and released glycosylated insulins permeate through the designed polymer membranes. The rate of release changed in response to changes in glucose concentration. Porous polylactic/glycolic acid and porous poly-HEMA membranes showed the fastest response and appeared to be suitable for the design of self-regulating insulin delivery systems.