Evaluation of Hydrogel Materials for Insulin Delivery in Closed Loop Treatment of Diabetes Mellitus

Hdl Handle:
http://hdl.handle.net/11285/572454
Title:
Evaluation of Hydrogel Materials for Insulin Delivery in Closed Loop Treatment of Diabetes Mellitus
Authors:
Sánchez Chávez, Irma Y.
Issue Date:
01/01/2008
Abstract:
The recovery of diminished or lost regulatory functions of physiological systems drives important research efforts in biomaterials and modeling and control engineering. Special interest is paid to diabetes mellitus because of its epidemic dimensions. Hydrogels provide the multifunctionality of smart materials and the applicability to medical regulatory systems, which is evaluated in this dissertation. The polymeric matrix of a hydrogel experiences reversible changes in volume in response to the pH of the environment, which depends on the presence of key metabolites in a physiological medium. The hydrogel swells due to internal repulsive electrostatic forces opening the matrix and releasing a preloaded drug. The contracted state of the hydrogel hinders the diffusion of the drug out of the polymer. In this work, poly(methacrylic acid-graft-ethylene glycol), P(MAA-g-EG), hydrogel membranes that incorporate glucose oxidase are used for insulin delivery. These glucose sensitive membranes are characterized and modeled for the closed loop treatment of type I diabetes mellitus. A physiological compartmental model is extended to represent the treatment system of a diabetic patient. Physical parameters of the P(MAA-g-EG) hydrogel material are obtained from experimental characterization and used as a basis to describe anionic and cationic hydrogels. The performance of the system closed by a hydrogel-based device is explored and compared to the dynamic behavior of a conventional scheme with an explicit controller element. A control algorithm for optimal insulin delivery in a type I diabetic patient is presented based on the linear quadratic control problem theory. The glucose-insulin dynamics is first represented by a linear model whose state variables are the glucose and the insulin concentrations in the blood. These variables allow the formulation of an appropriate cost function for a diabetes treatment in terms of the deviation from the normal glucose level and the dosage of exogenous insulin. The optimal control law is computed from this cost function under the servocontrol and regulatory approaches. Superior robustness of the regulatory control design is shown before random variations of the parameters of the linear physiological model. Further evaluation of the regulatory controller is realized with a high order nonlinear human glucose-insulin model. The control system performance can be improved by adjusting the weighting factors of the optimization problem according to the patients needs. The optimal controller produces a versatile insulin release profile in response to the variations of blood glucose concentration. Simulations demonstrate limitations in the range of swelling and contraction of hydrogels in a physiological environment due to factors such as the continuous presence of glucose in blood composition, the buffer characteristics of physiological fluids and the Donnan equilibrium effect. Results show that insulin loading efficiency is critical for the long term service of a hydrogel-based device, while delivery by a diffusion mechanism is convenient since it allows a basal insulin supply. The evaluation of hydrogel macrosystems prompts the consideration of the detected pros and contras in hydrogel microsystems, as well as in composite systems that may combine different materials and structures.
Keywords:
Hidrogel; Diabetes; Tratamiento
Degree Program:
Programa de Graduados en Ingeniería
Advisors:
Dr. Francisco ángel Bello
Committee Member / Sinodal:
Dr. Sergio Omar Martínez Chapa; Dr. Nicholas A. Peppas; Dr. Hugo Alberto Barera Saldaña; Dr. Blanca Hazalia Lapizco Encinas; Dr. Rubén Morales Menéndez
Degree Level:
Doctor en Ciencias de la Ingeniería con Especialidad en Mecatrónica
School:
Escuela de Ingeniería y Arquitectura
Campus Program:
Campus Monterrey
Discipline:
Ingeniería y Ciencias Aplicadas / Engineering & Applied Sciences
Appears in Collections:
Ciencias Exactas

Full metadata record

DC FieldValue Language
dc.contributor.advisorDr. Francisco ángel Belloes
dc.contributor.authorSánchez Chávez, Irma Y.es
dc.date.accessioned2015-08-17T11:32:36Zen
dc.date.available2015-08-17T11:32:36Zen
dc.date.issued01/01/2008-
dc.identifier.urihttp://hdl.handle.net/11285/572454en
dc.description.abstractThe recovery of diminished or lost regulatory functions of physiological systems drives important research efforts in biomaterials and modeling and control engineering. Special interest is paid to diabetes mellitus because of its epidemic dimensions. Hydrogels provide the multifunctionality of smart materials and the applicability to medical regulatory systems, which is evaluated in this dissertation. The polymeric matrix of a hydrogel experiences reversible changes in volume in response to the pH of the environment, which depends on the presence of key metabolites in a physiological medium. The hydrogel swells due to internal repulsive electrostatic forces opening the matrix and releasing a preloaded drug. The contracted state of the hydrogel hinders the diffusion of the drug out of the polymer. In this work, poly(methacrylic acid-graft-ethylene glycol), P(MAA-g-EG), hydrogel membranes that incorporate glucose oxidase are used for insulin delivery. These glucose sensitive membranes are characterized and modeled for the closed loop treatment of type I diabetes mellitus. A physiological compartmental model is extended to represent the treatment system of a diabetic patient. Physical parameters of the P(MAA-g-EG) hydrogel material are obtained from experimental characterization and used as a basis to describe anionic and cationic hydrogels. The performance of the system closed by a hydrogel-based device is explored and compared to the dynamic behavior of a conventional scheme with an explicit controller element. A control algorithm for optimal insulin delivery in a type I diabetic patient is presented based on the linear quadratic control problem theory. The glucose-insulin dynamics is first represented by a linear model whose state variables are the glucose and the insulin concentrations in the blood. These variables allow the formulation of an appropriate cost function for a diabetes treatment in terms of the deviation from the normal glucose level and the dosage of exogenous insulin. The optimal control law is computed from this cost function under the servocontrol and regulatory approaches. Superior robustness of the regulatory control design is shown before random variations of the parameters of the linear physiological model. Further evaluation of the regulatory controller is realized with a high order nonlinear human glucose-insulin model. The control system performance can be improved by adjusting the weighting factors of the optimization problem according to the patients needs. The optimal controller produces a versatile insulin release profile in response to the variations of blood glucose concentration. Simulations demonstrate limitations in the range of swelling and contraction of hydrogels in a physiological environment due to factors such as the continuous presence of glucose in blood composition, the buffer characteristics of physiological fluids and the Donnan equilibrium effect. Results show that insulin loading efficiency is critical for the long term service of a hydrogel-based device, while delivery by a diffusion mechanism is convenient since it allows a basal insulin supply. The evaluation of hydrogel macrosystems prompts the consideration of the detected pros and contras in hydrogel microsystems, as well as in composite systems that may combine different materials and structures.en
dc.language.isoenen
dc.rightsOpen Accessen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.titleEvaluation of Hydrogel Materials for Insulin Delivery in Closed Loop Treatment of Diabetes Mellitusen
dc.typeTesis de Doctoradoes
thesis.degree.grantorInstituto Tecnológico y de Estudios Superiores de Monterreyes
thesis.degree.levelDoctor en Ciencias de la Ingeniería con Especialidad en Mecatrónicaes
dc.contributor.committeememberDr. Sergio Omar Martínez Chapaes
dc.contributor.committeememberDr. Nicholas A. Peppases
dc.contributor.committeememberDr. Hugo Alberto Barera Saldañaes
dc.contributor.committeememberDr. Blanca Hazalia Lapizco Encinases
dc.contributor.committeememberDr. Rubén Morales Menéndezes
thesis.degree.disciplineEscuela de Ingeniería y Arquitecturaes
thesis.degree.namePrograma de Graduados en Ingenieríaes
dc.subject.keywordHidrogelen
dc.subject.keywordDiabetesen
dc.subject.keywordTratamientoen
thesis.degree.programCampus Monterreyes
dc.subject.disciplineIngeniería y Ciencias Aplicadas / Engineering & Applied Scienceses
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