Elastomers are largely developed for biomedical applications; however, little is reported on them although they are an effective and controllable delivery system for proteins. In the present study, we investigated the pharmacokinetics, biosecurity, and hypoglycemic effect of an insulin-loaded elastomer formulation in diabetic rats. Cylindrical insulin-loaded elastomers were fabricated using a UV cross-linking process based on methyl-acrylic-star-poly(ε-caprolactone-co-D,L-lactide) cyclic ester and methyl-bi-acrylic-poly(ε-caprolactone-b-polyethylene glycol-b-ε-caprolactone) (CLPEGCLMA). The encapsulated insulin was well protected during the formulation. An in vitro pharmacokinetic study revealed that the rate of insulin release from the elastomers was affected by the hydrophilicity/hydrophobicity of the system and controlled by the CLPEGCLMA (hydrophilic prepolymer) composition. It was observed that insulin release followed the Higuchi model. In addition, the more hydrophilic elastomers showed higher degradation rates in vivo. Furthermore, in the pharmacodynamic study, all the elastomers, except those that contained star-poly(ε-caprolactone-co-D,L-lactide) (number-average molecular weight, Mn), polyethylene glycol (PEG) (kMn), ε-caprolactone/PEG (mol/mol), and CLPEGCLMA (weight, %) at a ratio of 3432:10:20:30, respectively, decreased blood glucose concentration and maintained it at a stable level. It was observed that the hypoglycemic effect of the drug-loaded elastomers was directly proportional to the rate of in vitro insulin release; however, emaciation was not observed. Moreover, elastomers play a positive role in biosecurity. Therefore, the elastomers might be effective carriers for the delivery of peptide drugs in the form of implants.
Keywords: Biocompatibility; Controlled release; Degradable polymer; Elastomer; Insulin.
Copyright © 2017. Published by Elsevier B.V.