Therapeutic Potential Evaluation of Silk Sericin Stabilized Fisetin to Ulcerative Colitis.

Ulcerative colitis is a chronic inflammatory bowel disease with a high recurrence rate. Natural phytochemical compounds are increasingly being considered as preventative and supportive treatments for this condition. However, the poor water solubility and stability of many of these compounds limit their effectiveness in vivo. To address this issue, fisetin (FT), a natural phytochemical with poor solubility, is stabilized using silk sericin (SS) to create a composite (SS/FT). The therapeutic potential of the SS/FT on ulcerative colitis is extensively investigated, and the results showed that it effectively alleviated the body weight loss and colon length shortening induced by dextran sulfate sodium. Notably, SS/FT downregulated the immune response, decreased colonic histopathological lesions, and reduced the cGAS/STING signal activation. This suggests that SS/FT may offer a promising therapy for treating ulcerative colitis.

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.

In Vivo Characterizations of the Immune Properties of Sericin: An Ancient Material with Emerging Value in Biomedical Applications.

The biosafety of sericin remains controversial. The misunderstanding regarding sericin causing adverse biological responses have been clarified by extensively reviewing relevant literatures and experimentally demonstrating that sericin exhibits mild inflammatory responses, negligible allergenicity, and low immunogenicity in vivo. This study supports that sericin is biosafe as a natural biomaterial.

A study of long-term stability and antimicrobial activity of chlorhexidine, polyhexamethylene biguanide, and silver nanoparticle incorporated in sericin-based wound dressing.

In this study, three kinds of antiseptics which were 0.05% chlorhexidine, 0.2% polyhexamethylene biguanide (PHMB), or 200 ppm silver nanoparticle was introduced to incorporate in the sericin-based scaffold to produce the antimicrobial dressing for the treatment of infected chronic wound. The effects of antiseptic incorporation on the stability, release of sericin, and short-term and long-term (6 months) antimicrobial activity of the sericin dressing against gram-negative and gram-positive bacteria were investigated. We showed that the incorporation of each antiseptic did not have significant effect on the internal morphology (pore size ~ 73-105 µm), elasticity (Young's modulus ~ 200-500 kPa), and the sericin release behavior of the sericin-based dressing. The release of sericin from the dressing was prolonged over 120 h and thereafter. Comparing among three antiseptics, 0.05% chlorhexidine incorporated in the sericin dressing showed the highest immediate and long-term (6 months) antimicrobial effect (largest inhibition zone) against most bacteria either gram-positive or gram-negative bacteria. The in vivo safety test following ISO10993 standard (Biological evaluation of medical devices - Part 6: Tests for local effects after implantation) confirmed that the sericin dressing incorporating 0.05% chlorhexidine did not irritate to tissue, comparing with the commercial material used generally in clinic (Allevyn®, Smith & Nephew). We suggested the sericin dressing incorporating 0.05% chlorhexidine for the treatment of infected chronic wound. Chlorhexidine would reduce the risk of infection while the sericin may promote wound healing.

Evaluation of sericin/collagen membranes as prospective wound dressing biomaterial.

Sericin, a silk protein, has high potential for use in biomedical applications. In this study, wound dressing membranes of Sericin (S) and Collagen (C) were prepared by glutaraldehyde cross-linking at S/C; 2:1, 1:1, 1:2, and 0:1 weight ratios. They were stable in water for 4 weeks. However, increasing the proportion of sericin had decreasing effect on the membrane stability. Water swelling property of membranes was enhanced with sericin. The highest water swelling was obtained in 1:1 group (9.06 g/g), but increasing collagen or sericin content in the membranes had a diminishing effect. Highest water vapor transmission rate was obtained with 1:2 group (1013.80 g/m(2)/day). Oxygen permeability results showed that 1:2 (7.67 mg/L) and 2:1 (7.85 mg/L) S/C groups were better than the other groups. While sericin decreased the tensile strength and elongation of membranes, it increased modulus. Sericin also increased brittleness of membranes, but their UTS range (24.93-44.92 MPa) was still suitable for a wound dressing. Membranes were not penetrable to microorganisms. Cytotoxicity studies showed that fibroblasts and keratinocytes attached and gained their characteristic morphologies. They also proliferated on membranes significantly. After 1 week of subcutaneous implantation, a fibrous capsule formed around all membranes with an acute inflammation. Sericin containing membranes showed signs of degradation (at 2nd week), while collagen only membranes remained largely intact. Eventually, sericin containing membranes degraded in 3 weeks with moderate inflammatory response. Overall results suggest that sericin/collagen membranes would be favorable as wound dressing material when sericin ratio is less than or equal to the collagen component.