Alkanoylsucroses in nasal delivery of low molecular weight heparins: in-vivo absorption and reversibility studies in rats

Abstract

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.