Insulin delivery governed by covalently modified lectin-glycogen gels sensitive to glucose.
A glucose-sensitive gel formulation containing concanavalin A and glycogen has been reported previously. Precipitation resulting from the addition of concanavalin A to glycogen has been documented, but the formation of glucose-sensitive gels based on lectin-glycogen interactions is novel and used here in our studies. An improved in-vitro self-regulating drug-delivery system, using covalently modified glucose-sensitive gels based on concanavalin A and a polysaccharide displacement mechanism, is described. The successful use of the covalently modified gels addresses a problem identified previously where significant leaching of the mitogenic lectin from the gel membranes of non-coupled gels was encountered. Concanavalin A was covalently coupled to glycogen by use of derivatives of Schiff's bases. The resulting gels, like the non-coupled gels, were shown to undergo a gel-sol transformation in response to glucose. Insulin delivery was demonstrated using this covalently modified system in conditions of repeated glucose triggering at 20 degrees C and 37 degrees C. The magnitude of the response was less variable than for the dextran-based gels studied previously. The performance of this system has been improved in terms of concanavalin A leaching. This could, therefore, be used as the basis of the design of a self-regulating drug-delivery device for therapeutic agents used to treat diabetes mellitus.
Tanna
S
S
School of Pharmacy and Pharmaceutical Sciences, De Montfort University, The Gateway, Leicester, UK.
Taylor
M J
MJ
Adams
G
G
D001692:Biological Transport; D002626:Chemistry, Pharmaceutical; D003101:Collodion / Q000737:chemistry; D003208:Concanavalin A / Q000737:chemistry*; D005947:Glucose / Q000737:chemistry*; D006003:Glycogen / Q000737:chemistry*; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D007332:Insulin Infusion Systems; D037102:Lectins / Q000737:chemistry; D016062:Porosity
D007328:Insulin; D037102:Lectins; D003208:Concanavalin A; D003101:Collodion; D006003:Glycogen; D005947:Glucose