The Delivery of Insulin from Aqueous and Non-Aqueous Reservoirs Governed by a Glucose Sensitive Gel Membrane

Abstract

A self regulating delivery device, responsive to glucose, has been shown to operate successfully in vitro. This comprises a gel membrane which determines the delivery rate of insulin from a reservoir. The gel consists of a synthetic polysucrose and the lectin, concanavalin A. The mechanism is one of displacement of the branched polysaccharide from the lectin receptors by incoming glucose. The gel loses its high viscosity as a result but reforms on removal of glucose, thus providing the switch controlling the drug diffusion rate. The drug does not require to be chemically modified and thus the device is adaptable to other anti-hyperglycaemic drugs. However, results here indicate that the molecular weight of the solute may be an important parameter. Others include path length, gel formulation and temperature. It had been hypothesised that the reversal might be improved by the use of a non-aqueous reservoir of insulin. However, with the use of insulin, the switching off was found to be superior to that found with other test solutes used in previous studies, irrespective of the reservoir solvent. The advantages in the use of the non-aqueous system include, however, more reproducibility in the magnitude of response and a reduced temperature sensitivity.

Concanavalin A for in vivo glucose sensing: A biotoxicity review

“…March et al (2000) Glucose-sensitive sol-gel insulin release system Sephadex-bound (partial containment) -1-10 Pai et al (1992), Taylor et al (1995), Lee and Park (1996) sensor for in vivo glucose monitoring could remain functional in the body for 6-12 months or more. Despite this promise, the nature of most ConA sensors involves a risk, however small, that patient exposure to ConA may result.…”

The anti-diabetic potential of polysaccharides extracted from members of the cucurbit family: A review

“…Over many years research has been carried out to develop alternative novel drug delivery systems that would mimic the physiological environment by delivering insulin, in response to the blood glucose level. Formulations such as hydrogels, microcapsules, liposomes, and other soft technology systems as well as inserts and nanoparticles have been proposed (Taylor, Tanna, Taylor and Adams, 1995;Le Bourlais, Acar, Zia, Sado, Needham and Leverge, 1998;Gupta, Madan, Majumdar, and Maitra, 2000;Willoughby, Batterbury, and Kaye, 2002;Yadav, et. al., 2009;Adams, et.…”

UV Cross-Linked Dextran Methacrylate—Concanavalin A Methacrylamide Gel Materials for Self-Regulated Insulin Delivery

“…In previous work, we have described a basis for a selfregulating insulin delivery device that could be implanted in the intraperitoneal cavity Tanna, Taylor, & Adams, 1999;Taylor, Tanna, Taylor, & Adams, 1995). This delivery system is a reservoir device in which the rate control resides in a membrane comprising a glucose-sensitive gel material.…”

“…Variations are documented in which the polysaccharide has been replaced by semisynthetics such as polysucrose and glucosesubstituted acrylics (Valuev, Chupov, Stayton, & Plate, 1997). These materials have been used in sensor designs (Ballerstadt & Ehwald, 1994;Ehwald, Ballerstadt, & Dautzenberg, 1996) and as rate-determining membranes and matrices in potential drug delivery devices (Kim & Park, 2001c;Obaidat & Park, 1996;Taylor et al, 1995). In delivery systems, the drug leaves the device at a rate that is dependent on the receptor-polysaccharide linked status of the viscous layer and, thus, on the glucose concentration .…”