Enhanced model protein adsorption of nanoparticulate hydroxyapatite thin films on silk sericin and fibroin surfaces.

Hydroxyapatite coated metallic implants favorably combine the required biocompatibility with the mechanical properties. As an alternative to the industrial coating method of plasma spraying with inherently potential deleterious effects, sol-gel methods have attracted much attention. In this study, the effects of intermediate silk fibroin and silk sericin layers on the protein adsorption capacity of hydroxyapatite films formed by a particulate sol-gel method were determined experimentally. The preparation of the layered silk protein/hydroxyapatite structures on glass substrates, and the effects of the underlying silk proteins on the topography of the hydroxyapatite coatings were described. The topography of the hydroxyapatite layer fabricated on the silk sericin was such that the hydroxyapatite particles were oriented forming an oriented crystalline surface. The model protein (bovine serum albumin) adsorption increased to 2.62 µg/cm2 on the latter surface as compared to 1.37 µg/cm2 of hydroxyapatite on glass without an intermediate silk sericin layer. The BSA adsorption on glass (blank), glass/c-HAp, glass/m-HAp, glass/sericin/c-HAp, and glass/sericin/m-HAp substrates, reported as decrease in BSA concentration versus contact time.

Silk sericin has significantly hypoglycaemic effect in type 2 diabetic mice via anti-oxidation and anti-inflammation.

The sericin protein from silk-processing waste added to the normal diet at 0.8% (g%) level was administered orally to type 2 diabetic (T2D) mice to investigate its hypoglycaemic effects and mechanism. The oral protein is in the form of silk sericin hydrolysate, obtained from a boiling treatment of 0.025% calcium hydroxide solution. The protein significantly decreased fasting blood glucose, fasting plasma insulin, and glycosylated serum protein levels; improved oral glucose tolerance and insulin tolerance, and enhanced antioxidative activities. The protein could ameliorate the pathological damage in pancreatic ß-cells and the liver tissue. It enhanced the expression of key proteins and enzymes, including insulin receptor, insulin receptor substrate, PI3K, phosphorylated-AKT, hepatic kinase, GLUT4, glycogen synthase, GSK3ß, GLK, PFK1, PKM2, and AMPKα, which are related to insulin metabolism and glycolysis. The protein also reduced the expression of G6Pase, PCK, and ACC, which are related to gluconeogenesis and lipid metabolism in the liver, and decreased the expression of TNF-α, IL-6, P65, and IKKß related to inflammation. In general, sericin could maintain normal glucose levels and regulate insulin secretion, insulin and lipid metabolism, and inhibition of inflammation. Therefore, sericin protein could be developed into a novel functional health food with significantly hypoglycaemic effect.

Self-stabilized silk sericin-based nanoparticles: In vivo biocompatibility and reduced doxorubicin-induced toxicity.

A variety of colloid stabilizers and cryoprotectants confer improved nanoparticle (NP) colloidal stability and redisperability. However, discounted tumor targetability, delivery efficacy and possible side effects limit the application in vascular delivery of NPs. Here we present water-soluble silk sericin (SS) not only as a material for the preparation of NPs, but also both a dispersion stabilizer and a cryoprotectant. In the absence of any stabilizers, SS-based NPs (SSC@NPs) can resist the adsorption of serum proteins, preventing the formation of particle agglomerates. Following freeze-drying without addition of cryoprotectants, SSC@NPs powder can be easily resuspended into NP dispersion with a nearly monodispersed distribution. Additionally, SSC@NPs do not result in acute toxicity in mice at a dose of 400 mg/kg with a slow injection. Moreover, doxorubicin (DOX)-loaded SSC@NPs (DOX-SSC@NPs) diminish the biodistribution of DOX in the heart, mitigating DOX-induced cardiotoxicity of mice without compromising therapeutic efficacy. Our results suggest that the self-stabilized SSC@NPs could be a secure and effective drug carrier for intravenous administration when deprived of protective agents. STATEMENT OF SIGNIFICANCE: During manufacturing process such as freeze-drying, or interaction with complex fluids like blood, NPs for systemic drug delivery need to be highly dispersible and structurally intact. In this work, we have demonstrated the self-stability of SSC@NPs subjected to biological media and freeze-drying. This study represents the first work showing water-soluble SS could both act as a dispersion stabilizer and a cryoprotectant due to its hydrophilicity. Plus, good in vivo biocompatibility of SSC@NPs has been confirmed. Therefore, it may be promising that water-soluble SS can be generally used as a safe biomaterial against serum adsorption.