Recently, drug delivery materials have become the hotspot of medical study. Suitable delivery material plays an important role in constructing an excellent drug delivery system. Silk fibroin is a naturally occurring protein polymer with excellent biocompatibility, remarkable mechanical properties, biodegradability and outstanding processability. Due to its unique properties, silk fibroin has become a favorable carrier material for the incorporation and delivery of a range of therapeutic agents. Based on the structure and characteristics of silk fibroin, this article provides an overview of the recent research progress of silk fibroin used as drug delivery materials.
Calcium phosphate cement (CPC) has been widely used as bone fillers because of its excellent bioactivity and biocompatibility. Meanwhile, CPC is also an attractive candidate for the incorporation of drug or microspheres, because the preparing procedure avoids sintering and heating release. This paper summarizes the clinical applications of microspheres incorporated in CPC from the aspects of sustained drug release, accelerated degradation, porous structure and improved mechanical properties. The paper is aimed to analyze the methods and principles of microspheres loaded CPC, and so as to lay a foundation for the further research of improving and manufacturing the CPC with ideal properties.
With silk fibroin and vancomycin (VCM) as carrier and drug model, respectively, we prepared silk fibroin microspheres (SFM) with different concentration using the water-in-oil emulsion solvent diffusion method. We further developed VCM loaded calcium sulfate hemihydrates (CSH)/SFM artificial bone composites. In this study, surface morphology of the materials was observed using scanning electron microscope (SEM). Structure of the materials was studied with Fourier transform infrared spectroscopy (FTIR). Antibacterial activity of the materials was validated with the inhibition zone test. Drug release property of materials was evaluated using ultraviolet/visible spectrophotometry. Mechanical property of the materials was tested using computer-controlled electronic universal testing machine. The results showed that silk fibroin concentration had no significant effect on molecular conformation and antibacterial property of the SFM. The average diameter of SFM increased and the release rate decreased gradually as the silk fibroin concentration increased. The release rate decreased and the compressive fracture work increased as the silk fibroin concentration increased when adding SFM to CSH. This composite had partly corrected the disadvantages of CSH including the high brittleness and initial burst release. The research would have a good application foreground in the clinical treatment of infectious bone defect.
A multiple-stimuli-responsive drug-conjugated cross-linked micelles was prepared by radical copolymerization. The chemical structure, morphology, and size of the cross-linked micelles were characterized, and the drug loading of the micelle was calculated. The experimental results indicated that the hydrodynamic size of the drug-loaded micelles were about 100 nm, and the as prepared micelles could be degraded and swelled in presence of reducing glutathione (GSH). The low critical solution temperature (LCST) of the micelle was around 39.4℃. According to the experimental results, the micelles will shrink at temperature above the LCST. Subsequently, the accumulative drug release rate was up to 91.78% under acidic (pH 5.0), reductive (GSH 10 mmol/L) and high temperature (42.0℃) conditions mimicking the tumor microenvironment, while a relatively low release rate of 1.12% was observed without stimulation. The drug-conjugated cross-linked micelles showed a strong cell uptake behavior. In the cytotoxicity assay, the micelles exhibited effective anti-cancer activity and excellent biocompatibility. In brief, the experimental results show that the as-prepared drug-conjugated cross-linked micelle exhibits multiple stimuli-responsiveness, which holds great promise for anti-cancer drug delivery.
Curcumin-loaded poly (α-isobutyl cyanoacrylate) microspheres (Cur-HP-β-CD-PiBCA) were prepared by one-step emulsification with α-isobutyl cyanoacrylate as materials, poloxamer 188 as emulsifier, and curcumin complex with hydroxypropyl-β-cyclodextrin (Cur-HP-β-CD) as drug prepared by kneading method. Effects of emulsifier and drug concentration on microspheres size and distribution, drug loading and encapsulation efficiency were investigated in detail. And the curcumin release of drug-loaded microspheres was also studied. Results showed that as the emulsifier concentration increased from 0.01% to 0.07%, particle size of the drug-loaded microspheres decreased while particle size distribution, drug loading and entrapment efficiency increased. The optimized concentration of surfactant was 0.05%. With increasing the concentration of drug from 0.03% to 0.07%, drug loading of Cur-HP-β-CD-PiBCA increased, but encapsulation efficiency decreased. Additionally, the results of drug release experiments revealed that the higher drug loading of Cur-HP-β-CD-PiBCA was, the lower cumulative release percentage was. Drug-loading of cumulative inclusions in HP-β-CD by PiBCA can improve its wettability, and increase the degree of dissolution and bioavailability.
ObjectiveThe properties and characteristics of different types of silk fibroin (SF) drug-loaded sustained-release carriers and their effects on the drug release behavior were reviewed, and the existing problems and development prospects of SF drug-loaded sustained-release carriers in tissue engineering drug delivery system were discussed.MethodsThe literatures about drug-loaded SF sustained-release carriers in recent years were extensively consulted, and the types of sustained-release carriers, characteristics of drug release, range of applications, advantages and disadvantages, and solutions were summarized and analyzed.ResultsAt present, the SF drug-loaded sustained-release carriers are mainly divided into SF microparticles, SF scaffolds, SF membranes, SF hydrogels, SF nanofibers, SF sponges, and so on. These types of SF drug-loaded sustained-release carriers have their own advantages and problems, of which the most prominent problem is the burst release of drugs at the initial stage. While, the initial burst release of drugs can be effectively solved by improving the preparation process and adjusting the material ratio. Different types of drug-loaded sustained-release carriers can be prepared by combining different materials to achieve different application scopes and drug release behaviors under different conditions.ConclusionSF is a good drug-loaded carrier for tissue engineering, the burst release of drugs at the initial stage can be solved by improving the preparation process and changing the material structure; through the combination of the advantages of various types of SF drug-loaded sustained-release carriers, it is expected to prepare SF drug-loaded sustained-release carriers that meet different clinical needs.