title: Stability of PEGylated salmon calcitonin in nasal mucosa.
abstract: 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.
authors.affiliation: College of Pharmacy, SungKyunKwan University, 300 Chonchon-dong, Jangan-ku, Suwon City 440-746, Korea.
authors.forename: Dong Hee
authors.initials: DH
authors.lastname: Na
authors.forename: Yu Seok
authors.initials: YS
authors.lastname: Youn
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Park
authors.forename: Jeong Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Ock Ryun
authors.initials: OR
authors.lastname: Cho
authors.forename: Kang Ro
authors.initials: KR
authors.lastname: Lee
authors.forename: Sang Deuk
authors.initials: SD
authors.lastname: Lee
authors.forename: Sun Dong
authors.initials: SD
authors.lastname: Yoo
authors.forename: Patrick P
authors.initials: PP
authors.lastname: DeLuca
authors.forename: Kang Choon
authors.initials: KC
authors.lastname: Lee
mesh_terms: 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
chemical_list: D011092:Polyethylene Glycols; C028815:salmon calcitonin; D002116:Calcitonin