Novel iron-polysaccharide multilayered microcapsules for controlled insulin release.
Iron-polysaccharide complexes have been extensively used for the treatment of iron-deficiency anemia without side-effects. In this study, insulin-loaded microcapsules were prepared via layer-by-layer deposition of oppositely charged Fe(3+) and dextran sulfate (DS) onto the surface of insulin microparticles. Fe(3+) was combined with DS via both electrostatic interaction and chemical complexation process, leading to the formation of a stable complex of Fe(3+)/DS. Subsequently, protamine was used as the outermost layer of the insulin-loaded microcapsules to facilitate nuclear delivery. The sufficient charge reversal with successive deposition cycles and successful fabrication of hollow microcapsules provided strong evidence for the growth of (Fe(3+)/DS)(n) multilayer on the surface of microparticles. The experiments showed that the microcapsules successfully entrapped insulin with encapsulation efficiency of 70.56+/-0.97% and drug loading content of 46.15+/-0.97%. It was found that the release time and hypoglycemic effect increased as the number of deposited bilayers increased. The insulin-loaded microcapsules significantly improved glucose tolerance from 2 h (free insulin) to even 12 h (insulin-loaded microcapsules with 10 bilayers). Moreover, the microcapsules with protamine as the outermost layer displayed a prolonged and stable glucose-lowering profile over a period of over 6 h compared with Fe(3+) as the outermost layer. These findings indicate that such microcapsules can be a promising approach for the construction of an effective controlled release delivery system of insulin as well as other proteins with short half-life time.
Zheng
Jian
J
Nanomedicine and Biosensor Lab, Bio-X Center, Harbin Institute of Technology, Harbin 150080, China.
Yue
Xiuli
X
Dai
Zhifei
Z
Wang
Yang
Y
Liu
Shaoqin
S
Yan
Xiufeng
X
D000327:Adsorption / Q000187:drug effects; D000818:Animals; D002214:Capsules / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000494:pharmacology*; D016264:Dextran Sulfate / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007003:Hypoglycemia / Q000188:drug therapy; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007501:Iron / Q000737:chemistry*; D007700:Kinetics; D018613:Microscopy, Confocal; D051381:Rats
D002214:Capsules; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007328:Insulin; D016264:Dextran Sulfate; D007501:Iron