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Title: Lipidized salmon calcitonin for oral delivery
Keywords: salmon calcitonin, lipidization, delivery, oral, bioconjugation, activity
Issue Date: 5-Sep-2007
Citation: CHENG WEIQIANG (2007-09-05). Lipidized salmon calcitonin for oral delivery. ScholarBank@NUS Repository.
Abstract: The purpose of this project was to evaluate the hypothesis that lipid conjugation could improve the oral deliverability of salmon calcitonin (sCT). Five novel lipidized sCT conjugates were synthesized, of which Lipeo-sCT was a reversible conjugate; Mal-sCT was a non-reversible conjugate; and 1PEG-Mal-sCT, 2PEG-Mal-sCT and Mal-PL-sCT were Mal-sCT conjugates modified with PEG at different sites. These conjugates were characterized for their secondary structure, aggregation property, stability against intestinal and/or liver enzymes, cellular uptake and cytotoxicity in the Caco-2 cell model. In addition, the in-vivo activity and pharmacokinetic profiles of the conjugates were evaluated in the rat model. All the conjugates showed enhanced stability against the intestinal and liver enzymes, with higher cellular uptake observed for Mal-sCT than sCT in the Caco-2 cells. Subcutaneously injected Lipeo-sCT and Mal-sCT showed similar or extended hypocalcemic activities compared to sCT, while 1PEG-Mal-sCT and Mal-PL-sCT showed decreased hypocalcemic activity. 2PEG-Mal-sCT was biologically inactive. Despite these, none of the conjugates showed significant hypocalcemic activity when administered orally in the rat model.
Appears in Collections:Ph.D Theses (Open)

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