Stability of PEGylated salmon calcitonin in nasal mucosa.
The purpose of this study was to evaluate the stabilization of salmon calcitonin (sCT) by PEGylation in nasal mucosa. Degradation of native sCT in the homogenates of rat nasal mucosa was investigated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The initial cleavage of sCT was due to tryptic-like endopeptidase activity, and the subsequent degradation followed the sequential pattern of aminopeptidase activity. To prepare PEGylated sCT resistant to the proteolytic degradation, the lysine residues susceptible to tryptic activity were selectively PEGylated by controlling reaction pH. The PEGylated sCT showed strong resistance against enzymatic degradation in rat nasal mucosa, with 56-fold prolonged half-life compared with that of native sCT. In the MALDI-TOF MS spectrum, the PEGylated sCT did not show any degradation peak for incubation of 120 min in the homogenates of rat nasal mucosa. The improved stability may be responsible for enhancing nasal absorption of PEGylated sCT.
Na
Dong Hee
DH
College of Pharmacy, SungKyunKwan University, 300 Chonchon-dong, Jangan-ku, Suwon City 440-746, Korea.
Youn
Yu Seok
YS
Park
Eun Ji
EJ
Lee
Jeong Min
JM
Cho
Ock Ryun
OR
Lee
Kang Ro
KR
Lee
Sang Deuk
SD
Yoo
Sun Dong
SD
DeLuca
Patrick P
PP
Lee
Kang Choon
KC
D000818:Animals; D001711:Biotransformation; D002116:Calcitonin / Q000138:chemical synthesis / Q000378:metabolism* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D066298:In Vitro Techniques; D007536:Isomerism; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D011092:Polyethylene Glycols; C028815:salmon calcitonin; D002116:Calcitonin