Sulfated alginate based complex for sustained calcitonin delivery and enhanced osteogenesis

Abstract

Direct administration of salmon calcitonin (sCT) by subcutaneous or intramuscular injection is limited by its low efficiency. Drug delivery systems with sustained delivery properties and high bioactivity are urgently needed. For clinical applications an economical and effective carrier is required, which has been a challenge until now. In this study, a simple alginate/alginate sulfate-sCT (Alg/AlgS-sCT) complex was successfully constructed for sustained release of sCT. The negatively charged sulfate groups facilitate bonding with sCT, which avoids the burst release of sCT and extends the release time up to 15 d (it is only 2 d for pure sCT). More importantly, the bioactivity of the released sCT is not affected during such a long release time, suggesting a conformation similar to that of native sCT. In vitro analysis implies that the complex is biocompatible. Moreover, the combination of AlgS and sCT synergistically improves the osteogenic ability of MC3T3 cells, which show higher alkaline phosphatase levels and intracellular and extracellular calcium ion concentrations. The concentration of intracellular calcium ions is 5.26-fold higher than in the control group after 10 d of incubation. This simple yet effective system has potential applications in clinical trials and may inspire the design of other protein delivery systems.