INSULIN AND DIDECANOYL-L-ALPHA-PHOSPHATIDYLCHOLINE - INVITRO STUDY OF THE TRANSPORT THROUGH RABBIT NASAL MUCOSAL TISSUE

Transport over rabbit nasal mucosal tissue of insulin and the absorption enhancer didecanoyl-L-alpha-phosphatidylcholine (DDPC) from an aqueous nasal insulin preparation were studied in vitro using the Ussing chamber. The appearance of insulin at the serosal side is expressed as parts per thousand of the initial insulin concentration (8 mg/ml) at the mucosal side. Mean appearance rate was 0.67 +/- 0.53 parts per thousand h-1, equivalent to an apparent penetration coefficient (P(app)) of 0.37 x 10(-6) cm/s. Corrected for possible degradation and/or adsorption at the serosal side the value is 0.91 +/- 0.79 parts per thousand h-1 (P(app) = 0.50 x 10(-6) cm/s). Addition of 20 mg DDPC/ml increased the insulin concentration a factor of only 1.3-1.5, indicating that the Ussing chamber method may not always be able to identify penetration enhancers. The concentrations of insulin and DDPC at the mucosal side between 5 and 90 min were relatively constant, the average recovery being about 85%. No transport of DDPC through the nasal tissue, using an initial mucosal concentration of 20 mg/ml, was observed. The sensitivity of the whole system was 240 mug cm-2 h-1, or 1.2% h-1. P(app) is therefore lower than 0.33 X 10(-5) cm/s. The sensitivity of the system is limited by disappearance of DDPC at the serosal side.