EPITHELIAL TRANSPORT AND BIOAVAILABILITY OF INTRANASALLY ADMINISTEREDHUMAN GROWTH-HORMONE FORMULATED WITH THE ABSORPTION ENHANCERS DIDECANOYL-L-ALPHA-PHOSPHATIDYLCHOLINE AND ALPHA-CYCLODEXTRIN IN RABBITS

The transepithelial transport of biosynthetic human growth hormone (hG H) formulated with the absorption enhancers didecanoyl-L-alpha-phospha tidylcholine (DDPC) and alpha-cyclodextrin (alpha-CD) was studied afte r intranasal administration to rabbits. Plasma concentrations of the h ormone were determined until 240 min post administration by ELISA, and the absolute bioavailability was estimated to be in the vicinity of 2 0%. The localization of hGH was studied 15 min after application of th e powder formulation in the initial absorptive phase. To visualize the hormone, a two-step indirect immune-gold technique was used on semith in and ultrathin cryosections and Epon sections. Polyclonal rabbit ant i-hGH was used as primary antibody and gold-conjungated goat anti-rabb it IgG as secondary antibody, succeeded by silver enhancement. Growth hormone was mainly found in the cytoplasm and nuclei of ciliated cells , showing distinct morphological signs of early necrosis, and in lamin a propria, including the venules. Minute amounts of hGH were found in endocytotic Vesicles in morphologically normal epithelial cells and in the intercellular compartment. We conclude that the major transport r oute of hGH formulated with absorption enhancers DDPC and alpha-CD was transcellular through lethally damaged ciliated cells.