Alkanoylsucroses in nasal delivery of low molecular weight heparins: in-vivo absorption and reversibility studies in rats
Alkanoylsucroses in nasal delivery of low molecular weight heparins: in-vivo absorption and reversibility studies in rats
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DOI：
10.1211/0022357022377
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发表时间：
2004-01-01
影响因子：
3.3
通讯作者：
Ahsan, F
中科院分区：
文献类型：
--
作者：
Yang, TZ;Mustafa, F;Ahsan, F
已经研究了烷酰基蔗糖增强低分子量肝素 (LMWH) 鼻腔吸收的功效以及这些药物在鼻粘膜上的作用时间跨度。在这方面，将用烷酰基蔗糖配制的LMWH经鼻给予麻醉的雄性Sprague-Dawley大鼠，并通过测量血浆抗因子Xa活性来确定LMWH的吸收。通过体内可逆性研究研究了这些药物在给药部位的作用持续时间。将十二酰蔗糖的效力和功效与甘胆酸钠进行了比较。本研究中使用的烷酰基蔗糖包括十二酰基蔗糖、癸酰基蔗糖和辛酰基蔗糖。这些药物以剂量依赖性和链长度依赖性的方式增强依诺肝素的鼻吸收。在测试的药物中，十二酰蔗糖被发现在增强 LMWH 的鼻吸收方面最有效。与配制在盐水中的依诺肝素相比，用烷酰基蔗糖配制的依诺肝素的生物利用度增加了几倍。十二酰蔗糖的可逆性研究表明，烷酰蔗糖的作用随着时间的推移而逐渐消失，该药物在给药部位的作用持续时间为120-140分钟。发现十二酰蔗糖的效力是甘胆酸钠的两倍。总体而言，与烷酰基蔗糖共同给药可有效增强 LMWH 的鼻吸收，并且发现烷酰基蔗糖对鼻上皮的影响是可逆的。这些试剂的效力取决于它们的疏水链长度。
The efficacy of alkanoylsucroses in enhancing nasal absorption of low molecular weight heparin (LMWH) and the time span of action of these agents on the nasal membrane has been investigated. In this regard, LMWH formulated with alkanoylsucroses was administered nasally to anaesthetized male Sprague-Dawley rats and the absorption of LMWH was determined by measuring plasma anti-factor Xa activity. The duration of action of these agents at the site of administration was investigated by an in-vivo reversibility study. The potency and efficacy of dodecanoylsucrose was compared with that of sodium glycocholate. Alkanoylsucroses used in this study include dodecanoylsucrose, decanoylsucrose and octanoylsucrose. These agents enhance nasal absorption of enoxaparin in a dose-dependent and chain-length-dependent manner. Of the agents tested, dodecanoylsucrose was found to be the most potent in enhancing nasal absorption of LMWH. The bioavailability of enoxaparin formulated with alkanoylsucroses was increased by several folds compared with enoxaparin formulated in saline. The reversibility study with dodecanoylsucrose showed that the effect of alkanoylsucroses faded away with time and the duration of action of this agent at the site of administration was 120-140 min. Dodecanoylsucrose was found to be twice as potent as sodium glycocholate. Overall, the nasal absorption of LMWH was effectively enhanced by co-administration of alkanoylsucroses and the effect of alkanoylsucroses on nasal epithelium was found to be reversible. The potency of these agents depends on their hydrophobic chain lengths.