A new natural angelica polysaccharide based colon-specific drug delivery system.
Colon-specific drug delivery systems are clinically necessary to treat colon diseases locally while minimizing systemic side effects. In this study, we extracted angelica polysaccharide from fresh roots of Angelica sinensis Diels and analyzed the monosaccharide components. With succinate as a cross-linker and angelica polysaccharide as a drug carrier, a dexamethasone-polysaccharide conjugate was synthesized. The amount of dexamethasone (Dex) loaded in the dexamethasone-polysaccharide conjugate was 14.13/100 mg. The newly synthesized dexamethasone-polysaccharide conjugate was found to greatly reduce systemic absorption of Dex and effectively deliver Dex to the large intestine. When dexamethasone-polysaccharide conjugate was used to treat TNBS-induced ulcerative colitis in rats by gavage, the ulcerative area of the colon and the colonic myeloperoxidase (MPO) activity was reduced in a dose-dependent manner. There was no effects on spleen weight, thymus weight, or peripheral blood lymphocyte count (0.25 micromol kg(-1) day(-1)). These results indicate that the dexamethasone-polysaccharide conjugate has a therapeutic effect on TNBS-induced ulcerative colitis in rats, while simultaneously reducing the systemic immunosuppression caused by Dex. Thus, the angelica polysaccharide was a promising colon-specific drug carrier, and the new dexamethasone-polysaccharide conjugate may yield a potential drug for the treatment of human inflammatory bowel disease.
Zhou
Siyuan
S
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Zhang
Bangle
B
Liu
Xinyou
X
Teng
Zenghui
Z
Huan
Menglei
M
Yang
Tiehong
T
Yang
Zhifu
Z
Jia
Min
M
Mei
Qibing
Q
D029969:Angelica / Q000737:chemistry*; D000818:Animals; D002241:Carbohydrates / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000473:pathology; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D004337:Drug Carriers; D016503:Drug Delivery Systems; D008970:Molecular Weight; D010936:Plant Extracts / Q000737:chemistry / Q000493:pharmacokinetics; D010940:Plant Proteins / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry* / Q000302:isolation & purification / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared; D014302:Trinitrobenzenesulfonic Acid
D002241:Carbohydrates; D004337:Drug Carriers; D010936:Plant Extracts; D010940:Plant Proteins; D011134:Polysaccharides; D012997:Solvents; D014302:Trinitrobenzenesulfonic Acid