Osteoporosis therapy consists of inhibiting the osteoclasts' activity and promoting osteoblasts' osteogenesis. Salmon calcitonin (sCT) could realize both requirements, however, it is limited by the low bioavailability caused by fibrillation. Supramolecular assembly of sCT and biocompatible agents into nanoassemblies provides an opportunity to overcome these shortcomings. Herein, we used a facile method to fabricate salmon calcitonin-aspartame (sCT-APM) nanoassemblies. Supramolecular interactions could not only delay fibrillation time (from 36.9 h to 50.4 h), but also achieve sustained sCT release. Moreover, sCT-APM showed good biocompatibility and higher osteoinductive capacity than free sCT, revealing an osteogenesis improvement effect. Moreover, in vivo studies showed that sCT-APM has enhanced relative bioavailability (2.42-fold of sCT) and increased relative therapeutic efficacy (3.55-fold of sCT) through subcutaneous injection. These findings provide a convenient alternative strategy for osteoporosis therapy via supramolecular assemblies.
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