Absorption of salmon calcitonin

Sinko PJ, Lee YH, Makhey V, Leesman GD, Sutyak JP, Yu H, Perry B, Smith CL, Hu P, Wagner EJ, Falzone LM, Mcwhorter LT, Gilligan JP and Stern W (1999) Biopharmaceutical Approaches for Developing and Assessing Oral Peptide Delivery Strategies and Systems In Vitro Permeability and In Vivo Oral Absorption of Salmon Calcitonin (Set). Pharm Res 16 pp 527-533. 

Hinchcliffe, M., I. Jabbal-Gill, and A. Smith. 2005. Effect of chitosan on the intranasal absorption of salmon calcitonin in sheep. J Pharm Pharmacol 57 681. 

Calcitonin is another compound that was often incorporated into nanoparticles to enhance its oral absorption. Takeuchi et al. (2001) developed Elcato-nin-loaded PLGA nanospheres coated with chitosan, observing a reduction of blood calcium level. Sakuma et al. (2002) hypothesizes that both mucoadhesion of nanoparticles incorporating salmon calcitonin into the GI mucosa (Sakuma et al. 1999,2002) and increase in the stability of salmon calcitonin in the GI tract (Sakuma et al. 1997) result in the improvement of salmon calcitonin absorption. Moreover, chitosan-PEG nanocapsules increased the absorption of salmon calcitonin (Prego et al. 2006). 

Sinswat, P. Tengamnuay, P. Enhancing effect of chitosan on nasal absorption of salmon calcitonin in rats comparison with hydroxypropyl- and dimethyl-beta-cyclodextrins. Int. J. Pharm. 2003, 257 (1-2), 15-22. 

Morimoto, K., Katsumata, H., Yabuta, T., et al. (2000). Gelatin microspheres as a pulmonary delivery system Evaluation of salmon calcitonin absorption. J. Pharm. Pharmacol., 52, 611-617. 

After they had received 100 units of salmon calcitonin subcutaneously for 3 days, four patients had a 30% mean reduction in serum lithium concentration, which was attributed to reduced absorption and/or increased renal excretion (23). 

Shah, R.B., A. Palamakula, and M.A. Khan. 2004. Cytotoxicity evaluation of enzyme inhibitors and absorption enhancers in Caco-2 cells for oral delivery of salmon calcitonin. J Pharm Sci 93 1070. 

Shin, B.S., et al. 2004. Nasal absorption and pharmacokinetic disposition of salmon calcitonin modified with low molecular weight polyethylene glycol. Chem Pharm Bull 52 957. 

Kobayashi, S., S. Kondo, and K. Juni. 1994. Study on pulmonary delivery of salmon calcitonin in rats effects of protease inhibitors and absorption enhancers. Pharm. Res. 11 1239-1243. 

Another approach to enzyme inhibition is to manipulate the pH to inactivate local digestive enzymes. Lee et al. conducted studies demonstrating that oral absorption properties of salmon calcitonin can be modulated by changing intestinal pH. Reducing the intestinal pH in the GI tract, increased absorption of the intact peptide.34 A sufficient amount of a pH-lowering buffer that lowers local intestinal pH to values below 4.5 can deactivate trypsin, chymotrypsin, and elastase. 

Torres-Lugo, M., Garcia, M., Record, R., Peppas, N.A. pH sensitive hydrogels as GI tract absorption enhancers Transport mechanism of salmon calcitonin and other model molecules using caco-2 cell model. Biotech. Prog., 18, 612, 2002. 

Tengamnuay, S. R, Mitra, A. K. (1997]. Chitosans as nasal absorption enhancers of salmon calcitonin Comparison with hydroiqrpropyl-and dimethyl-b-cyclodextrins, Pharm. Res., 14, SI 29. 

Calcitonin (Miacalcin, Miacalcin Nasal Spray) is a synthetic 32-amino acid polypeptide that is identical to salmon calcitonin. Salmon calcitonin is more potent than human calcitonin because of its higher affinity for the human calcitonin receptor and its slower metabolic clearance. Administration is by subcutaneous or intramuscular injection or by nasal spray. The absorption of the nasal form is slower than that of the parenteral routes. 

Calcitonin is a peptide hormone produced in the thyroid gland that serves to lower serum calcium and phosphate levels by inhibiting bone resorption. Calcitonin has been used in the treatment of a variety of diseases, such as primary hyperparathyroidism, Paget s disease, and postmenopausal osteoporosis [99,100]. Salmon calcitonin has a longer half-life than human calcitonin. Salmon calcitonin, 3.6 kDa, is available as a nasal formulation that contains only benzalkonium chloride as a preservative, without an absorption enhancer, and as a parenteral product for injection. The direct effect of benzalkonium chloride on the nasal mucosa is under... 

Rhinocort is a commercially available mucoadhesive transnasal powder preparation of beclomethasone dipropionate with hydroxypropyl cellulose (HPC) as a gelforming drug carrier developed by Suzuki and Makino [49], The HPC has been shown to promote the absorption of low-molecular-weight drugs, but it was not that effective with a peptide drug salmon calcitonin. Microcrystalline cellulose has been shown to be effective for the promotion of absorption of calcitonin in humans, producing about 10% bioavailability with rapid absorption onset [49], In the study... 

Sakuma, S., Suzuki, N., Kikuchi, H., Hiwatari, K. I., Arikawa, K., Kishida, A. and Akashi, M., Absorption enhancement of orally administered salmon calcitonin by polystyrene nanoparticles having poly(V-isopropylacrylamide) branches on their surfaces, Int. J. Pharm., 158, 69-78 (1997). 

Research on oral liposomal delivery systems has moved forward with the development of polymer-modified liposomes. For example, targeted PEGylated liposomes furnished with folic acid for oral delivery were promising, showing enhanced permeability of dextran (used as a marker) across Caco-2 cell monolayers (Anderson et al., 1999). PEG and chitosan-coated lipid nanoparticles were constmcted as oral delivery systems for salmon calcitonin (sCT). The PEG-coated nanoparticles did not alter the transepithelial electrical resistance of Caco-2 cell monolayers, while the chitosan-coated nanoparticles showed a dose-dependent increase in the permeability of dextran across the monolayers (Garcia-Fuentes et al., 2005). It demonstrated that the favourable interaction of the chitosan-coated nanoparticles with intestinal mucosa, together with their permeation enhancing characteristics, could improve the oral absorption of sCT. 

C. Sinsuebpol, J. Chatchawalsaisin, and Kulvanich, Preparation and in vivo absorption evaluation of spray dried powders containing salmon calcitonin loaded chitosan nanoparticles for pulmonary delivery. (1177-8881 (Electronic)). 

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