Composite Separable Microneedles for Transdermal Delivery and Controlled Release of Salmon Calcitonin for Osteoporosis Therapy

A composite separable microneedles (MNs) system consisting of silk fibroin (SF) needle tips and hyaluronic acid (HA) base is developed for transdermal delivery of salmon calcitonin (sCT) for therapy of osteoporosis. Poly(ethylene glycol) (PEG) is used to modulate the conformation structure of SF to achieve controllable sustained release of sCT. The prepared MNs can effectively penetrate the skin stratum corneum. After application to the skin, the HA base is dissolved within 2 min, allowing these SF drug depots to be implanted into the skin for controllable sustained release of sCT. The release kinetics of sCT can be controlled by regulating the conformation of SF with PEG and the interaction between sCT peptide and SF proteins. Compared with traditional needle injection, delivery of sCT using optimized HA-PEG/SF MNs shows better trabecular bone repair for ovariectomized-induced osteoporosis in mice. The proposed MNs system provides a new noninjection strategy for therapy of osteoporosis.