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Biodegradable Nanoparticles Containing Protein‐fatty Acid Complexes For Oral Delivery Of Salmon Calcitonin

H. Yoo, T. G. Park
Published 2004 · Chemistry

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Abstract Biodegradable nanoparticles containing salmon calcitonin (sCT) were formulated using protein–fatty acid complexes, and their in vitro transport against a Caco‐2 cell monolayer and the extent of in vivo oral uptake were assessed. Positively charged sCT was hydrophobically ion paired to form physical complexes with fatty acid, phospholipid, and surfactant. Among the complexes, sodium oleate was used to form sCT–oleate complexes, which were characterized and formulated into biodegradable poly(lactic‐ co ‐glycolic acid) (PLGA) nanoparticles. Endocytosis of sCT nanoparticles by Caco‐2 cells was studied by flow cytometry. Transcytosis of sCT across the Caco‐2 monolayer was also quantitated by an ELISA method. The sCT nanoparticles were orally administered to Sprague‐Dawley rats, and serum sCT was monitored. Biodegradable polymeric nanoparticles containing a loading amount of sCT as high as 2.7% (w/w) were prepared based on the complexation of sCT with sodium oleate. A greater amount of sCT nanoparticles could be delivered into Caco‐2 cells compared with free sCT, and sCT could also be transported from the apical side to the basolateral side of the Caco‐2 monolayer. In vivo experiments using a rat animal model showed the possibility of oral uptake of sCT. This study showed that physical complexation of sCT with amphiphilic molecules enabled the formation of sCT‐loaded PLGA nanoparticles at a high loading efficiency and that sCT–PLGA nanoparticles were transported across the Caco‐2 cell monolayer and were readily taken up in vivo following oral admistration. © 2004 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:488–495, 2004
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