Cetin Meltem, Youn Yu Seok, Capan Yilmaz, Lee Kang Choon
Department of Pharmaceutical Technology, Faculty of Pharmacy, Ataturk University, 25240 Erzurum, Turkey.
AAPS PharmSciTech. 2008;9(4):1191-7. doi: 10.1208/s12249-008-9165-2. Epub 2008 Dec 11.
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.
本研究旨在制备并表征用于口服给药的生物素化鲑鱼降钙素（sCT），并评估生物素化sCT在大鼠体内的降钙作用。采用高效液相色谱（HPLC）和基质辅助激光解吸电离飞行时间质谱（MALDITOF-MS）对生物素化sCT进行表征。考察生物素化对sCT跨Caco-2细胞单层通透性的影响。在大鼠体内测定其降钙作用。通过反相HPLC分离单生物素化sCT和双生物素化sCT。单生物素化sCT和双生物素化sCT的分子量分别测定为3660.5 Da和3900.2 Da。观察到生物素化sCT跨Caco-2细胞单层的通透性与sCT相比有显著增强。空肠内（ij）给予单生物素化sCT和双生物素化sCT导致血清钙水平持续降低，给药4小时和6小时后最大降低幅度（% max(d)）分别为21.6%和30%。sCT的生物素共轭可能是提高sCT口服生物利用度并实现持续降钙效果的一种有前景的策略。
