Insulin delivery systems

Reservoir designs, heat pipe, 73 236 Reservoir drug delivery systems, 9 77 Reservoir insulin delivery systems, 9 69 Reservoirs... 

A. H. Krauland, V. M. Leitner, V. Grabovac, and A. Bernkop-Schnurch. In vivo evaluation of a nasal insulin delivery system based on thiolated chitosan. J Pharm Sci 95 2463-2472 (2006). 

Wainstein J, Metzger M, Wexler ID, Cohen J, Raz I. The use of continuous insulin delivery systems in severely insulin-resistant patients. Diabetes Care 2001 24(7) 1299. 

Morishita, M., et al. 2006. Novel oral insulin delivery systems based on complexation polymer hydrogels Single and multiple administration studies in type 1 and 2 diabetic rats. J Control Release 110 587. 

Figure 1. Schematic representation of insulin delivery systems.

FIGURE 40.2 Example Data Flow for Insulin Delivery System. 

The requirements for the insulin delivery system would include specific patient-safety needs such as ... 

A risk analysis is then required to confirm these safety requirements can be met, that the medical device will not malfunction, and that a safe state is maintained in relation to patient health. For the insulin delivery system a safe state is a shut-down state where no insulin is delivered. Over a short period this will not pose a threat to the diabetic s health. ... 

An insulin delivery system, for example, might have the following hazards and associated classes ... 

As described previously, the specific interactions between enzymes and lectins with carbohydrates have been evaluated for use in insulin delivery systems based on responses to chemical and biochemical stimuli. These include pH, changes in specific ion concentration, and specific molecular recognition events [15]. 

Further development of the self-regulating insulin delivery system has utilized the complex of glycosylated insulin-concanavalin A, which is encapsulated inside a polymer membrane. As glucose penetrates into the system, it activates the release of glycosylated insulin from the complex for a controlled release from the system (Fig. 28). The amount of insulin released is thus self-regulated by the concentration of glucose that has penetrated into the insulin delivery system. 

Fig. 27 Cross-sectional view of a bioresponsive insulin delivery system, a feedback-regulated drug delivery system, showing the glucose oxidase-entrapped hydrogel membrane constructed from amine-containing hydrophilic pol5mier. The mechanism of insulin release, in response to the influx of glucose, is also illustrated. (From Ref. l)...

Marishita M, Goto T, Peppas NA, et al. Mucosal insulin delivery systems based on complexation polymer hydrogels effect of particle size on insulin enteral absorption. / Control Release 2004 97(1) 67-78. 

Renard, E., Costalat, G., Chevassus, H., and Bringer, J. (2006) Artificial beta-cell clinical experience toward an implantable closed-loop insulin delivery system. Diabetes ef Metabolism, 32 (5), 497-502. 

Protein Hormones. Glycosylated insulin has been prepared (D21) and its biologic function shown to be reduced by 20%. However, the life of protein hormones in vivo is short, and so that negligible in vivo glycosylation occurs. The use of glycosylated insulin complexed to con-canavalin A in a closed-loop insulin delivery system has been described (B27) it presented stability advantages over conventional insulins in these situations. 

B27. Brownlee, M., and Cerami, A., Glyc-osylated insulin complexed to concanavalin A Biochemical basis for a closed-loop insulin delivery system. Diabetes 32, 499-504... 

While poly (ortho esters) are add-sensitive, their sensitivity is not sufficient for use in a self-regulated insulin delivery system. However, when a diol contains a tertiary amine in the backbone is used, the pH-sensitivity is enormously increased. The structure of a polymer from 3,9-bis (ethylidene 2,4,8,10-tetraoxas-piro [5,5] undecane) and /V-methyldiethanolamine is shown in Scheme 17. 

Fig. 19. Schematic representation of proposed insulin delivery system [38]. Reprinted with permission...

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