Oral insulin delivery using P(MAA-g-EG) hydrogels: effects of network morphology on insulin delivery characteristics.
Hydrogels of poly(methacrylic acid-g-ethylene glycol) were prepared using different reaction water contents in order to vary the network mesh size, swelling behavior and insulin loading/release kinetics. Gels prepared with greater reaction solvent contents swelled to a greater degree and had a larger network mesh size. All of the hydrogels were able to incorporate insulin and protected it from release in acidic media. At higher pH (7.4), the release rates increased with reaction solvent content. Using a closed loop animal model, all of the insulin loaded formulations produced significant insulin absorption in the upper small intestine combined with hypoglycemic effects. In these studies, bioavailabilities ranged from 4.6% to 7.2% and were dependent on reaction solvent content.
Nakamura
Koji
K
Department of Chemical Engineering, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104, USA.
Murray
Robert J
RJ
Joseph
Jeffrey I
JI
Peppas
Nicholas A
NA
Morishita
Mariko
M
Lowman
Anthony M
AM
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose; D002417:Cattle; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D020100:Hydrogels / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D007082:Ileum / Q000187:drug effects / Q000502:physiology / Q000601:surgery; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008422:Materials Testing / Q000379:methods; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics; D011108:Polymers / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011109:Polymethacrylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013678:Technology, Pharmaceutical / Q000379:methods
D001786:Blood Glucose; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D007328:Insulin; D011108:Polymers; D011109:Polymethacrylic Acids; C098758:tetraethyleneglycol dimethacrylate; D011092:Polyethylene Glycols