Enhanced rectal and nasal absorption of human epidermal growth factor by combined use of the absorption promoter and the synthetic polymer in rats.
Previously, the presence of sodium carboxymethylcellulose (CMC Na) in addition to an absorption promoter, sodium caprate (C10 Na), in the dosing solution was found to be necessary for the enhancement of the rectal absorption of human epidermal growth factor (hEGF). In the present study, other synthetic polymers and absorption promoters were examined for their ability to enhance the rectal and nasal absorption of hEGF in rats. The effect of polymers in combined use with 100 mM C10 Na on the rectal absorption of hEGF was in the following order: 1% methylcellulose 1% hydroxypropylmethylcellulose 0.1% polyacrylic acid 1% CMC Na. Other absorption promoters such as N-lauroyl-alanine (C12-A) and dihydroxy-bile salts also enhanced the rectal absorption of hEGF in combined use with CMC Na. In order to confirm the increased rectal absorption of hEGF, the disappearance of hEGF from the rectal loop was examined. When hEGF in a 1% CMC Na solution (200 ug/kg) was administered in the rectal loop, the disappearance percent of hEGF during 60 min was 13.9% of the dose, although hEGF was not detected in the plasma. The presence of promoters such as 10 mM C10 Na or 15 mM C12-A in 1% CMC Na increased the disappearance percent to about 50% in a dosing range of hEGF from 100 to 500 ug/kg. On the other hand, a markedly enhanced nasal absorption of hEGF by 100 mM C10 Na was observed even in the absence of any polymer in a dising solution. However, addition of CMC Na into the dosing solution accelerated the rate of nasal absorption of hEGF in early phase.(ABSTRACT TRUNCATED AT 250 WORDS)
Murakami
T
T
Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Japan.
Kishimoto
M
M
Kawakita
H
H
Kisaki
M
M
Kojima
Y
Y
Higashi
Y
Y
Amagase
H
H
Fuwa
T
T
Yata
N
N
D000180:Acrylic Resins / Q000494:pharmacology; D000281:Administration, Intranasal; D000285:Administration, Rectal; D000818:Animals; D003652:Decanoic Acids / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005079:Excipients; D006801:Humans; D065347:Hypromellose Derivatives; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000494:pharmacology; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism*; D011108:Polymers / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000180:Acrylic Resins; D003652:Decanoic Acids; D005079:Excipients; D011108:Polymers; D065347:Hypromellose Derivatives; C031071:decanoic acid; C006903:carbopol 940; D004815:Epidermal Growth Factor; D008747:Methylcellulose