Nasal absorption enhancement of insulin by sodium deoxycholate in combination with cyclodextrins

To evaluate the nasal absorption enhancement of insulin by sodium deoxychol ate (SDC) in combination with cyclodextrins ( CD). METHODS: The concentrati on of glucose in blood was measured. Scanning electron microscopy technique was used to investigate the effect of enhancers on the nasal mucocilia. Th e effect of SDC in combination with CD on the leucine aminopeptidase ( LAP) activity in the nasal mucosa was observed. RESULTS: Intranasal administrat ion of insulin (4 U/kg) along with 0.75 % SDC/beta -CD at a molar ratio of 1:2 slowly decreased the blood glucose levels of ruts. The minimal blood gl ucose level was (72.6 +/- 2.1) % of baseline, and which was lasted for 3 h. Though the decrement of blood glucose in 0.75 % SDC/beta -CD (1: 2) treate d group was less than that in 0.75 % SDC treated group, there was no signif icant difference between the two groups in AOC(0-t) values (P > 0.05). SDC (0.01 %) solution did not have any absorption prompting effect. Scanning el ectron microscopy investigation showed that 0.75 % SDC/beta -CD (1:2) solut ion had no marked damage on rat nasal mucosa 4 h after nasal administration , while 0.01 % SDC still had some damage on the rat nasal mucosa. The inhib itory effect of SDC on the LAP activity was decreased from 89.2 % to 69.2 % , 71.5 %, 60.4 %, and 61.3 % in 0.75 % SDC/beta -CD (1:1), 0.75 % SDC/beta -CD (1:2), 0.75 % SDC/DM-beta -CD (1:1), and 0.75 % SDC/DM-beta -CD (1:2) t reated group, respectively. CONCLUSION: Combining beta -CD with SDC lowered the serious nasal ciliotoxicity of SDC and had a marked absorption promoti ng effect, which was not due to low concentration of SDC but was related wi th the inhibition of LAP activity.