Complexation hydrogels for intestinal delivery of interferon beta and calcitonin.
Recent studies have suggested that complexation hydrogels poly(methacrylic acid-g-ethylene glycol) (henceforth designated as P(MAA-g-EG)) exhibit high insulin incorporation efficiency, rapid insulin release in the intestine based on their pH-dependent complexation properties, enzyme-inhibiting effects and mucoadhesive characteristics. Therefore, they are promising carriers for insulin delivery via an oral route. As we designed these hydrogels as carriers suitable for oral administration of various peptide/protein drugs, in this study we aimed at investigating the applicability of P(MAA-g-EG) hydrogels to improving the intestinal absorption of various peptide/protein drugs. High loading efficiency into hydrogels was observed for insulin, calcitonin, and interferon beta. In addition, polymer microparticles loaded with calcitonin and interferon beta exhibited complexation/decomplexation and pH-sensitive release behavior. The molecular weight and chemical structure appeared to affect the efficiency of loading and release depending on the peptides and proteins. Furthermore, a drastic reduction of plasma calcium concentration accompanied by calcium absorption and a dose-dependent enhancement of plasma interferon beta concentration were observed after the administration of particles loaded with calcitonin or interferon beta into closed rat ileal segments. These findings indicate that P(MAA-g-EG) hydrogels are promising carriers for administration of various peptides and proteins via an oral route.
Kamei
Noriyasu
N
Department of Pharmaceutics, Hoshi University, Shinagawa, Tokyo, Japan.
Morishita
Mariko
M
Chiba
Hitomi
H
Kavimandan
Nikhil J
NJ
Peppas
Nicholas A
NA
Takayama
Kozo
K
D000818:Animals; D002116:Calcitonin / Q000008:administration & dosage* / Q000378:metabolism; D002118:Calcium / Q000097:blood; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D016899:Interferon-beta / Q000008:administration & dosage* / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D011109:Polymethacrylic Acids / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004337:Drug Carriers; D020100:Hydrogels; D011109:Polymethacrylic Acids; C099679:poly(methacrylic acid-ethylene glycol); D011092:Polyethylene Glycols; D016899:Interferon-beta; D002116:Calcitonin; D002118:Calcium