title: Absorption enhancing effects of chitosan oligomers on the intestinal absorption of low molecular weight heparin in rats.
abstract: Absorption enhancing effects of chitosan oligomers with different type and varying concentration on the intestinal absorption of low molecular weight heparin (LMWH) were examined by an in situ closed loop method in different intestinal sections of rats. Chitosan hexamer with the optimal concentration of 0.5% (w/v) showed the highest absorption enhancing ability both in the small intestine and large intestine. The membrane toxicities of chitosan oligomers were evaluated by morphological observation and determining the biological markers including amount of protein and activity of lactate dehydrogenase (LDH) released from intestinal epithelium cells. There was no obvious change both in levels of protein and LDH and morphology in the intestinal membrane between control and various chitosan oligomers groups, suggesting that chitosan oligomers did not induce any significant membrane damage to the intestinal epithelium. In addition, zeta potentials became less negative and amount of free LMWH gradually decreased when various chitosan oligomers were added to LMWH solution, revealing that electrostatic interaction between positively charged chitosan oligomers and negative LMWH was included in the absorption enhancing mechanism of chitosan oligomers. In conclusion, chitosan oligomers, especially chitosan hexamer, are safe and efficient absorption enhancers and can be used promisingly to improve oral absorption of LMWH.
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Mi
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Yayu
authors.initials: Y
authors.lastname: Huo
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xing
authors.affiliation: Department of Pharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yamamoto
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: gaoyangyang@mail.xjtu.edu.cn.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage* / Q000737:chemistry; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D015951:Factor Xa; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000737:chemistry; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007420:Intestine, Large / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D007421:Intestine, Small / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D017207:Rats, Sprague-Dawley
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D048271:Chitosan; D007770:L-Lactate Dehydrogenase; D015951:Factor Xa
keywords: Absorption enhancer; Chitosan oligomers; Electrostatic interaction; Intestinal absorption; Low molecular weight heparin (LMWH); Membrane toxicity