Mechanochemical approaches to self-regulating insulin pump design

Abstract Wearable and implantable insulin delivery devices have been proposed by many groups to replace periodic subcutaneous insulin injection. The rationale behind this work lies in the lack of correspondence between insulin and glucose disposition resulting from subcutaneous administration compared with that occurring after pancreatic insulin release. We briefly review features of insulin and glucose disposition processes that impact the design of artificial insulin delivery systems, enabling advantages and disadvantages of currently pursued strategies (electromechanical, biochemical, chemical, mechanochemical) to be identified. We also propose two implantable self-regulating insulin pumps whose action depends on the expansion and contraction of certain pH-sensitive hydrogel membranes that respond to changes in glucose concentration via enzymatic conversion of glucose to gluconic acid. It is shown that the dynamics of pH-sensitive volume changes favor one pump design, based on direct conversion of changes in glucose concentration to mechanical force, over the other, which is an osmotic pump whose semipermeable membrane's permeability to water is sensitive to glucose concentration.

[1]  R. Siegel,et al.  Dynamic pH-dependent swelling properties of a hydrophobic polyelectrolyte gel , 1988 .

[2]  H. Yasuda,et al.  Diffusive and hydraulic permeabilities of water in water‐swollen polymer membranes , 1971 .

[3]  Toyoichi Tanaka,et al.  Kinetics of discontinuous volume-phase transition of gels , 1988 .

[4]  A. Cerami,et al.  A glucose-controlled insulin-delivery system: semisynthetic insulin bound to lectin. , 1979, Science.

[5]  H. Landahl,et al.  Role of rate of change of glucose concentration as a signal for insulin release. , 1977, Endocrinology.

[6]  A M Albisser,et al.  A circulation and organs model for insulin dynamics. , 1979, The American journal of physiology.

[7]  J. Kost,et al.  Magnetically enhanced insulin release in diabetic rats. , 1987, Journal of biomedical materials research.

[8]  Buddy D. Ratner,et al.  Glucose sensitive membranes for controlled delivery of insulin: Insulin transport studies , 1985 .

[9]  J. Feijen,et al.  Self-regulating insulin delivery systems I. Synthesis and characterization of glycosylated insulin , 1984 .

[10]  L. John,et al.  Blood glucose control in diabetic rats by transdermal iontophoretic delivery of insulin , 1988 .

[11]  S. W. Kim,et al.  Self-reguiating isnssultn delivery systems II. In vitro studies , 1984 .

[12]  J. Heller Chemically self-regulated drug delivery systems , 1988 .

[13]  B D Ratner,et al.  Glucose-sensitive membranes containing glucose oxidase: activity, swelling, and permeability studies. , 1985, Journal of biomedical materials research.

[14]  W. Schenk,et al.  Does Physiological Blood Glucose Control Require an Adaptive Control Strategy? , 1987, IEEE Transactions on Biomedical Engineering.

[15]  S. W. Kim,et al.  Self-regulating insulin delivery systems: III. In vivo studies , 1985 .

[16]  A. Grodzinsky,et al.  Proton diffusion reaction in a protein polyelectrolyte membrane and the kinetics of electromechanical forces , 1981 .

[17]  Ronald A. Siegel,et al.  pH-Dependent Equilibrium Swelling Properties of Hydrophobic Polyelectrolyte Copolymer Gels , 1988 .

[18]  Toyoichi Tanaka Kinetics of phase transition in polymer gels , 1986 .

[19]  T. Okano,et al.  Thermo-sensitive polymers as on-off switches for drug release , 1987 .

[20]  W. Spencer,et al.  A Review of Programmed Insulin Delivery Systems , 1981, IEEE Transactions on Biomedical Engineering.

[21]  A. Cerami,et al.  Glycosylated Insulin Complexed to Concanavalin A: Biochemical Basis for a Closed-Loop Insulin Delivery System , 1983, Diabetes.

[22]  R. L. Broughton,et al.  Hydrophilic polyacrylates for the microencapsulation of fibroblasts or pancreatic islets , 1987 .

[23]  J. Halter,et al.  Insulin secretion in diabetes mellitus. , 1981, The American journal of medicine.

[24]  Isao Shinohara,et al.  Glucose Induced Permeation Control of Insulin through a Complex Membrane Consisting of Immobilized Glucose Oxidase and a Poly(amine) , 1984 .

[25]  F. Lim,et al.  Microencapsulated islets as bioartificial endocrine pancreas. , 1980, Science.

[26]  Claudio Cobelli,et al.  Evaluation of Portal/Peripheral Route and of Algorithms for Insulin Delivery in the Closed-Loop Control of Glucose in Diabetes - A Modeling Study , 1983, IEEE Transactions on Biomedical Engineering.

[27]  H. Iwata,et al.  Preparation and properties of novel environment-sensitive membranes prepared by graft polymerization onto a porous membrane , 1988 .

[28]  N. L. Ricker,et al.  Theoretical and experimental studies of glucose sensitive membranes , 1987 .

[29]  R. Langer,et al.  Enzymatically controlled drug delivery. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Kazuhiko Ishihara,et al.  Glucose‐responsive insulin release from polymer capsule1 , 1986 .