Enhancing effect of chitosan on nasal absorption of salmon calcitonin in rats:: comparison with hydroxypropyl- and dimethyl-β-cyclodextrins
Enhancing effect of chitosan on nasal absorption of salmon calcitonin in rats:: comparison with hydroxypropyl- and dimethyl-β-cyclodextrins
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DOI：
10.1016/s0378-5173(03)00090-5
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发表时间：
2003-05-12
影响因子：
5.8
通讯作者：
Tengamnuay, P
中科院分区：
文献类型：
--
作者：
Sinswat, P;Tengamnuay, P
研究了壳聚糖的游离胺（CS J）和谷氨酸盐（CS G）对鲑鱼降钙素（sCT）在大鼠鼻腔吸收的促进作用。随后将结果与最常研究的增强剂之一β-环糊精进行了比较。以10 IU/kg的剂量经鼻施用在等渗磷酸盐缓冲液（IPB; pH 3.0-6.0）中含有sCT和壳聚糖（0- 1.25%w/v）的溶液。通过计算血浆钙的总下降百分比（%D）来确定每只sCT治疗大鼠的血浆钙降低作用。CS J显示增加%D作为溶液的pH值降低，根据增加的电离和水合的游离胺壳聚糖在更酸性的pH值。然而，CS G显示增加%D随着pH值的增加，与最大hypocalcoherent效果观察到在pH 6.0。在其最适pH值（CS J为4.0，CS G为6.0）下，两种壳聚糖的吸收促进作用在0.25 - 1.0%范围内呈浓度依赖性，在1.25%时趋于平稳。使用特异性RIA，与静脉给药相比，1% CS J、5%二甲基-β-环糊精（DM-β-CD）和对照组（单独鼻内sCT）sCT的绝对生物利用度分别为2.45、1.91和1.22%。尽管与静脉给药相比，绝对鼻内生物利用度似乎较低，但与对照组相比，纳入1% CS J导致血浆sCT的AUC（0-180）增加2倍。添加5%的DM-β-CD也导致吸收比对照组增加1.56倍。所有促进剂均表现出明显的吸收促进作用（P
Two types of chitosan, i.e. the free amine (CS J) and the glutamate salt (CS G), were evaluated for their enhancing effect on in vivo nasal absorption of salmon calcitonin (sCT) in rats. The results were subsequently compared with beta-cyclodextrins, one of the most commonly studied enhancers. Solutions containing sCT and chitosan (0-1.25% w/v) in isotonic phosphate buffers (IPB; pH 3.0-6.0) were nasally administered at the dose of 10 IU/kg. The plasma calcium lowering effect in each sCT-treated rat was determined by calculating the total percent decrease in plasma calcium (%D). CS J showed an increase in %D as the solution pH was decreased in accordance with the increased ionization and hydration of the free amine chitosan at the more acidic pH. However, CS G showed an increase in %D with increasing pH, with maximum hypocalcemic effect observed at pH 6.0. At their optimal pH (4.0 for CS J and 6.0 for CS G), the absorption enhancing effect of both chitosans was concentration dependent from 0.25 to 1.0% and leveled off at 1.25%. Using specific RIA, the absolute bioavailability of sCT after comparison with i.v. administration was determined to be 2.45, 1.91, and 1.22% for 1% CS J, 5% dimethyl-beta-cyclodextrin (DM-beta-CD) and control group (intranasal (in) sCT alone), respectively. Although the absolute nasal bioavailability seemed to be low when compared to the i.v. administration, the inclusion of 1% CS J resulted in two-fold increase in the AUC(0-180) of plasma sCT relative to that of the control group. Addition of 5% DM-beta-CD also led to 1.56-fold increase in absorption over the control group. All the enhancers showed significant absorption enhancement (P