Efficiency of cell-penetrating peptides on the nasal and intestinal absorption of therapeutic peptides and proteins.
The purpose of our study was to investigate the potential of cell-penetrating peptides; penetratin as novel delivery vector, on the systemic absorption of therapeutic peptides and proteins across different mucosal administration sites. The absorption-enhancing feasibility of l- and d-penetratin (0.5mM) was used for glucagon-like peptide-1 (GLP-1), and exendin-4 as novel antidiabetic therapy, in addition to interferon-beta (IFN-beta) as protein biotherapeutic model from nasal and intestinal route of administration was evaluated as first time in rats. Nasal route is the most feasible for the delivery of therapeutic peptides coadministered with penetratin whereas the intestinal route appears to be more restricted. The absolute bioavailability (BA (%)) values depend on the physichochemical characters of drugs, stereoisomer character of penetratin, and site of administration. Penetratin significantly increased the nasal more than intestinal absorption of GLP-1 and exendin-4, as the BA for nasal and intestinal administration of GLP-1 was 15.9% and 5%, and for exendin-4 were 7.7% and 1.8%, respectively. Moreover, the BA of IFN-beta coadministered with penetratin was 11.1% and 0.17% for nasal and intestinal administration, respectively. From these findings, penetratin is a promising carrier for transmucosal delivery of therapeutic peptides and macromolecules as an alternative to conventional parenteral routes.
Khafagy
El-Sayed
el-S
Department of Pharmaceutics, Hoshi University, Shinagawa, Tokyo, Japan.
Morishita
Mariko
M
Kamei
Noriyasu
N
Eda
Yoshimi
Y
Ikeno
Yohei
Y
Takayama
Kozo
K
D000281:Administration, Intranasal; D000465:Algorithms; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002352:Carrier Proteins / Q000737:chemistry / Q000494:pharmacology*; D002404:Catheterization; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000493:pharmacokinetics*; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics*; D007082:Ileum / Q000187:drug effects; D016899:Interferon-beta / Q000097:blood / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007536:Isomerism; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014688:Venoms / Q000097:blood / Q000493:pharmacokinetics*
D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D016899:Interferon-beta; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; C414409:penetratin