Effects of surfactants and protease inhibitors on nasal absorption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rats.
The effects of various surfactants and protease inhibitors on the nasal absorption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) were examined in rats. No effects of bile salts and acids such as sodium glycocholate or taurocholic acid, amphoteric surfactants such as lauryldimethyl betaine, or anionic surfactants such as sodium lauryl sulfate on the absorption were found at a concentration of 1%. But non-ionic surfactants with hydrophile/lipophile balance (HLB) of 13 to 18 increased the total leukocyte numbers maximally by about 250% as a relative increase ratio to the control without surfactants. The increase in the plasma rhG-CSF concentration was obviously observed only in the presence of non-ionic surfactants, and in particular, the effects of Laureth-9 on the increase in total leukocyte numbers and plasma rhG-CSF concentration were maximal. In the presence of various kinds of protease inhibitors, the increasing effect of rhG-CSF on the total leukocyte numbers was not changed. Consequently, it is considered that the permeation of rhG-CSF through the nasal epithelium can be improved by non-ionic surfactants, but the effect of a protease inhibitor is smaller than that of the surfactant.
Machida
M
M
Formulation Technology Lab., Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
Sano
K
K
Arakawa
M
M
Hayashi
M
M
Awazu
S
S
D000042:Absorption / Q000187:drug effects; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001414:Bacitracin / Q000494:pharmacology; D001622:Betaine / Q000031:analogs & derivatives / Q000494:pharmacology; D003902:Detergents / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D006000:Glycocholic Acid / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism; D010664:Phenylmethylsulfonyl Fluoride / Q000031:analogs & derivatives / Q000494:pharmacology; D000077423:Polidocanol; D011092:Polyethylene Glycols / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology*; D013656:Taurocholic Acid / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology
D003902:Detergents; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D013501:Surface-Active Agents; D000077423:Polidocanol; D001414:Bacitracin; D016179:Granulocyte Colony-Stimulating Factor; D012967:Sodium Dodecyl Sulfate; D001622:Betaine; D011092:Polyethylene Glycols; D010664:Phenylmethylsulfonyl Fluoride; D013656:Taurocholic Acid; C034252:laurylbetain; C027226:(4-amidinophenyl)methanesulfonyl fluoride; D007611:Aprotinin; D014357:Trypsin; D006000:Glycocholic Acid; D007930:Leucine; C012211:ubenimex; D005033:Ethylmaleimide