Nasal absorption enhancement of insulin by sodium deoxycholate in combination with cyclodextrins.
OBJECTIVE
To evaluate the nasal absorption enhancement of insulin by sodium deoxycholate (SDC) in combination with cyclodextrins (CD).


METHODS
The concentration of glucose in blood was measured. Scanning electron microscopy technique was used to investigate the effect of enhancers on the nasal mucocilia. The effect of SDC in combination with CD on the leucine aminopeptidase (LAP) activity in the nasal mucosa was observed.


RESULTS
Intranasal administration 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 rats. The minimal blood glucose 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) treated group was less than that in 0.75 % SDC treated group, there was no significant difference between the two groups in AOC0- t values (P > 0.05). SDC (0.01 %) solution did not have any absorption prompting effect. Scanning electron microscopy investigation showed that 0.75 % SDC/beta-CD (1 : 2) solution 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 inhibitory 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) treated group, respectively.


CONCLUSIONS
Combining beta-CD with SDC lowered the serious nasal ciliotoxicity of SDC and had a marked absorption promoting effect, which was not due to low concentration of SDC but was related with the inhibition of LAP activity.
Zhang
Y
Y
Division of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, China.
Jiang
X G
XG
Yao
J
J
D000042:Absorption / Q000187:drug effects; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002923:Cilia / Q000187:drug effects / Q000378:metabolism; D003505:Cyclodextrins / Q000494:pharmacology*; D003840:Deoxycholic Acid / Q000494:pharmacology*; D004347:Drug Interactions; D004357:Drug Synergism; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics; D007328:Insulin / Q000493:pharmacokinetics*; D007931:Leucyl Aminopeptidase / Q000378:metabolism; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D003505:Cyclodextrins; D007004:Hypoglycemic Agents; D007328:Insulin; D003840:Deoxycholic Acid; D007931:Leucyl Aminopeptidase