Chitosan oligomers as potential and safe absorption enhancers for improving the pulmonary absorption of interferon-alpha in rats.
Effects of chitosan oligomers on pulmonary absorption of interferon-alpha (IFN) were examined by means of an in vivo pulmonary absorption experiment. Chitosan oligomers used in this study were chitosan dimer, tetramer, hexamer, and water-soluble (WS) chitosan. A significant increase in serum IFN concentrations was observed after intratracheal administration of IFN with these oligomers. Of these chitosan oligomers, 0.5% w/v chitosan hexamer appeared to be more effective in enhancing the pulmonary absorption of IFN than other oligomers at the same concentration, and the AUC value of IFN with chitosan hexamer increased 2.6-fold as compared with the control. On the other hand, chitosan polymers, which have relatively high molecular weights (22-96 kDa), were not effective in enhancing the pulmonary absorption of IFN due to their low solubility in water. Additionally, the effect of different concentrations (0.1%-1% w/v) of chitosan hexamer on the pulmonary absorption of IFN was studied. Of these different concentrations of chitosan hexamers, the highest AUC value of IFN was obtained in the presence of 0.5% w/v chitosan hexamer. Furthermore, chitosan oligomers did not cause any membrane damage to the rat pulmonary tissues, as determined by leakage of protein and lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid. Therefore, these findings indicated that the use of chitosan oligomers would be a promising approach for improving of the pulmonary absorption of biologically active peptides including IFN.
Yamada
Keigo
K
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
Odomi
Masaaki
M
Okada
Naoki
N
Fujita
Takuya
T
Yamamoto
Akira
A
D000042:Absorption / Q000187:drug effects; D000818:Animals; D019540:Area Under Curve; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology; D001682:Biological Availability; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016898:Interferon-alpha / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
D001672:Biocompatible Materials; D016898:Interferon-alpha; D048271:Chitosan