Preparation and characterization of salmon calcitonin-biotin conjugates.
This study was performed to prepare and characterize the biotinylated Salmon calcitonin (sCT) for oral delivery and evaluate the hypocalcemic effect of biotinylated-sCTs in rats. Biotinylated sCTs was characterized by using high performance liquid chromatography (HPLC) and MALDITOF-MS. The effect of biotinylation on permeability across Caco-2 cell monolayers was examined. Their hypocalcemic effect was determined in rats. Mono- and di-bio-sCTs were separated by reverse phase HPLC. The molecular weights of mono-bio-sCT and di-bio-sCT were determined to be 3,660.5 and 3,900.2 Da, respectively. The permeability of biotinylated-sCTs across Caco-2 cell monolayers was observed with a significant enhancement compared with sCT. Intrajejunal (ij) administration of mono-bio-sCT and di-bio-sCT resulted in sustained reduction in serum calcium levels, with a maximum reduction (% max(d)) of 21.6% and 30% after 4 h and 6 h of application, respectively. The biotin conjugation of sCT may be a promising strategy for increasing the oral bioavailability of sCT and achieving sustained calcium-lowering effects.
Cetin
Meltem
M
Department of Pharmaceutical Technology, Faculty of Pharmacy, Ataturk University, 25240 Erzurum, Turkey. melcetin@atauni.edu.tr
Youn
Yu Seok
YS
Capan
Yilmaz
Y
Lee
Kang Choon
KC
D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D001710:Biotin / Q000008:administration & dosage / Q000737:chemistry*; D018938:Caco-2 Cells; D002116:Calcitonin / Q000008:administration & dosage / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D001710:Biotin; C028815:salmon calcitonin; D002116:Calcitonin