In a series of models for acute and chronic inflammatory pain, the new morphine derivate AS006 (AlcaSynn GmbH, Austria), has been shown to have excellent efficacy. The activation of central m-opioid receptors is associated with adverse actions, including respiratory depression, sedation and physical dependence. In contrast, the hydrophilic AS006 is an effective opioid analgesic which does not cross the blood brain barrier and selectively activates peripheral opioid receptors on sensory neurons in injured tissues. Therefore, AS006 is of great interest to be administered orally.

Methods: 

To open the paracellular transport pathway for AS006, chitosan was employed. Human colon epithelial cells were grown on permeable supports until confluency and mounted in Ussing chambers for measurement of transepithelial resistance and apical-to-serosal flux of AS006

Results: 

A liquid chromatography-tandem mass spectrometry method was developed and validated for quantification of AS006 in HEPES buffered samples taken from the basolateral side of the epithelial cell layers. Flux measurements revealed an increased permeability for AS006 in combination with chitosan, indicating an increased paracellular passage of AS006.

Conclusions: 

In vitro Ussing chamber measurements suggest AS006 as a promising analgesic for targeted activation of peripheral opioid receptors. AS006 can cross the epithelial barrier when co-applied with the absorption enhancer chitosan but does not cross the blood brain barrier.