Covalent coupling of concanavalin A to a Carbopol 934P and 941P carrier in glucose-sensitive gels for delivery of insulin.
A novel glucose-sensitive gel formulation, containing concanavalin A and specific polysaccharides, was stabilised via covalent coupling to two structurally different carbomers. The bonding was done to minimise leaching of gel components thereby preventing toxicity and preserving the working mechanism of the gel. Increased gel stability was introduced by covalently bonding amine groups present on the lysine residues of concanavalin A to carboxylic moieties on Carbopol 934P NF and 941P NF using carbodiimide chemistry. The introduction of dextran then produced a glucose-sensitive formulation that transformed from gel to sol in the presence of free glucose. Rheological examination of glucose-sensitive gels stabilised in this way and containing varying concentrations of glucose was conducted with a cone and plate viscometer used in continual rotation mode. A decrease in viscosity over the chosen glucose concentration range was exhibited by both carbomer-stabilised formulations. The subsequent testing of such formulations in in-vitro diffusion experiments revealed that the leaching of concanavalin A from the covalently coupled gels is restricted significantly with respect to non-coupled formulations. In addition, insulin delivery in response to glucose in the physiologically relevant glucose concentration range has been demonstrated using the carbomer-stabilised gels at 37 degrees C. The performance of this self-regulating drug delivery system has been improved in terms of increased gel stability with reduced component leaching.
Tanna
S
S
School of Pharmacy and Pharmaceutical Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, UK. stanna@dmu.ac.uk
Sahota
T
T
Clark
J
J
Taylor
M J
MJ
D000179:Acrylates / Q000737:chemistry*; D003208:Concanavalin A / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004355:Drug Stability; D005782:Gels; D005947:Glucose / Q000737:chemistry*; D007328:Insulin / Q000008:administration & dosage*; D037102:Lectins / Q000737:chemistry; D012212:Rheology; D013997:Time Factors; D014783:Viscosity
D000179:Acrylates; D004337:Drug Carriers; D005782:Gels; D007328:Insulin; D037102:Lectins; D003208:Concanavalin A; D005947:Glucose; C453622:carbopol 934P