Hydroxyapatite Regulated By Silk Fibroin And Silk Nanofiber As Carriers For Controlled Drug Release

Silk fibroin (SF) has been extensvely studied as biomedical material due to itsremarkable mechanical properties, structural controllability, excellent biocompatibility anddegradability. As drug delivery carrier and mineralization template, silk also has promisingfuture in drug delivery, optical material and tissue regeneration applications. As theprincipal component of human bones and teeth, hydroxyapatite (HA) is widely studied andused in bone and dental repair applications. Furthermore, hydroxyapatite-based compositenanoparticles have also been attractive candidates for therapeutic delivery applications.However, the preparation of colloidally stable hydroxyapatite particles with a well-definedsize and morphology remains a challenge. In the present study, we used silk fibroin withuniform nano-structure as template to control hydroxyapatite formation.First, silk fibroin solution was incubated at60oC for24h. The HA/SF composite wasobtained by a Ca(NO3)2suspension and (NH4)2HPO4-SF mixed solution using biomimeticsynthesis method. Herein, the mass proportion of the inorganic component to organiccomponent is2:8. The results showed that pin-like HA particles changed into rice-likeHA/SF particles after silk fibroin addtion. Finally formed homogenous nanoparticles withexcellent dispersibility in water.Secondly, the model drugs, rhodamine B and fluorescein isothiocyanate labeledbovine serum albumin (FITC-BSA), were carried into the HA nanoparticles. Resultsshowed that the model drugs could be loaded to the carrier and released slowly within120hours. The carrier has pH-dependent solubility, where the drug release amount can becontrolled by adjusting the pH of release medium. The pH-sensitive property will be usefulin vitro and in vivo applications. Considering biodegradability and impressivebiocompatibility of HA/SF composites and their mild preparation conditions, HA/SF isexpected to become excellent carriers for medicines.Furthermore, we prepared silk nanofibers with the length of1-2μm through regulatingself-assembly of silk fibroin under different temperatures and concentrations. The nanofibers could be broken into short length by ultrasonic method and then re-grew toform longer nanofibers after culture process at60oC, which is a useful process forinjectable carrier. Rhodamine B was used as model drug. The result demonstrated that themodel drug can be released slowly and steadily in the tested96hours.In summary, we successfully prepared HA nanoparticles by using silk fibroin withuniform nano-structures. Then we explored application possibility of the HA/SFnanopaticles and silk nanofibers as potential drug carriers.