Flash Fabrication of Orally Targeted Nanocomplexes for Improved Transport of Salmon Calcitonin across the Intestine

Salmon calcitonin (sCT) is a potent calcium-regulating peptide hormone and widely applied for the treatment of some bone diseases clinically. However, the therapeutic usefulness of sCT is hindered by the frequent injection required owing to its short plasma half-life and therapeutic need for high dose. Oral delivery is a popular modality of administration for patients because of its convenience to self-administration and high patient compliance, while oral administered sCT remains a great challenge currently due to the existence of multiple barriers in gastrointestinal (GI) tract. Here, we introduced an orally targeted delivery system to increase the transport of sCT across the intestine through both paracellular permeation route and bile acid pathway. In this system, sCT-based glycol chitosan-taurocholic acid conjugate (GC-T)/dextran sulfate (DS) ternary nanocomplexes (NC-T) were produced by flash nanocomplexation (FNC) process in a kinetically controlled mode. The optimized NC-T exhibited well-controlle...