Complexation hydrogels for intestinal delivery of interferon β and calcitonin

• Published in: Journal of controlled release 2009-03, Vol.134 (2), p.98-102
• Main Authors: Kamei, Noriyasu, Morishita, Mariko, Chiba, Hitomi, Kavimandan, Nikhil J., Peppas, Nicholas A., Takayama, Kozo
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Calcitonin; Calcitonin - administration & dosage; Calcitonin - metabolism; Calcium - blood; Complexation polymers; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Carriers - pharmacology; Drug delivery system; General pharmacology; Hydrogels - administration & dosage; Hydrogels - chemistry; Hydrogels - pharmacology; Interferon β; Interferon-beta - administration & dosage; Interferon-beta - metabolism; Intestinal absorption; Intestinal Absorption - drug effects; Male; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - chemistry; Polyethylene Glycols - pharmacology; Polymethacrylic Acids - administration & dosage; Polymethacrylic Acids - chemistry; Polymethacrylic Acids - pharmacology; Rats; Rats, Sprague-Dawley
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2008.11.014

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 β. In addition, polymer microparticles loaded with calcitonin and interferon β 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 β concentration were observed after the administration of particles loaded with calcitonin or interferon β 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. The absorption of interferon β following ileal administration of various doses of interferon β loaded P(MAA-g-EG). Interferon-loaded P(MAA-g-EG) (●) or interferon β solution (○). [Display omitted]