Dual drug delivery system of teicoplanin and phenamil based on pH-sensitive silk fibroin/sodium alginate hydrogel scaffold for treating chronic bone infection.

For effective treatment of infected bone, it is essential to use local drug delivery systems with the ability to deliver both antibiotics and osteoinductive factors. Herein, a pH-sensitive silk fibroin (SF)/sodium alginate (SA) hydrogel scaffolds containing teicoplanin (TEC) and phenamil (PM) loaded SF nanoparticles (PMSFNPS) are introduced for treating chronic osteomyelitis. The TEC and PM showed a sustained- and pH-sensitive release behavior from SF/SA hydrogel. The higher release rate was seen in an alkaline pH in comparison to neutral and acidic pH during 10 days. The eluted TEC maintained its antibacterial activity of >75 % during 35 days and in three different pH values (5.5, 7.4, and 8.5). The cellular study indicated that the scaffolds containing PMSFNPs could promote the cell viability, ALP activity, and matrix mineralization. Moreover, the in vivo effectiveness of hydrogel scaffolds were analyzed with radiography, histological and Immunohistochemistry evaluations. The lower infection and higher regeneration were observed in methicillin-resistant Staphylococcus aureus (MRSA) infected rat bone treated with hydrogel scaffold containing PMSFNPs and TEC compared to other groups. Consequently, this dual-drug delivery system could be a hopeful approach for effective treatment of chronic bone infection.

Evaluation of E. coli Nissle1917 derived metabolites in modulating key mediator genes of the TLR signaling pathway.

OBJECTIVE: Gut-microbiota plays key roles in many aspects like the health and illness of humans. It's well proved that modification of gut microbiota by probiotics is useful for improving inflammatory bowel disease (IBD) conditions. According to recent studies, different types of bacterial metabolites can affect immune cells and inflammation conditions. The present study aimed to evaluate the anti-inflammatory effects of metabolites of E. coli Nissle1917. RESULTS: The cell-free supernatant could modulate TNF-α production and affected many crucial mediators in the Toll-like receptor (TLR) signaling pathway. Also, supernatant showed significant dose-dependent properties in this regard. In this study, the TLR signaling pathway was found among probable mechanisms by which probiotics can affect inflammatory situations. These findings provide additional evidence on the use of probiotic metabolites for inhibiting and down-regulating numerous key mediator factors in the TLR signaling pathway. Aberrant or dysfunctional TLR signaling contributes to the development of acute and chronic intestinal inflammatory pathways in IBD. Therefore, finding a component that can affect this process might be considered for therapeutic targets in IBD patients.

Dual drug delivery system based on pH-sensitive silk fibroin/alginate nanoparticles entrapped in PNIPAM hydrogel for treating severe infected burn wound.

Herein, the pH-sensitive vancomycin (VANCO) loaded silk fibroin-sodium alginate nanoparticles (NPs) embedded in poly(N-isopropylacrylamide) (PNIPAM) hydrogel containing epidermal growth factor (EGF) are introduced for treating chronic burn wound infections. The hybrid system was developed to control the release rates of an antibiotic and growth factor for optimal treatment of burn infections. VANCO had a pH responsive release behavior from the nanoparticle (NP) and showed higher release rate in an alkaline pH compared to the neutral pH during 10 d. About 30% of EGF was also released from the hydrogel within 20 d. The released VANCO and EGF preserved their bioactivity more than ∼ 80%. The suitable physico-chemical properties and cellular behaviors of PNIPAM hydrogel supported the proliferation and growth of the fibroblast cells. Furthermore, the higher re-epithelialization with good wound contraction rate, neovascular formation, and expression of transforming growth factor-beta were observed in S. aureus infected rat burn wound by using the hydrogel containing VANCO and EGF compared with untreated wounds and hydrogel alone. The wound infection was also significantly reduced in the groups treated with the hydrogels containing VANCO. Overall, in vitro and in vivo results suggested that developed hybrid system would be a promising construct to treat severe wound infection.

Preparation of a Codelivery System Based on Vancomycin/Silk Scaffold Containing Silk Nanoparticle Loaded VEGF.

One of the main challenges of using biomaterials for inducing bone regeneration is the bacterial resistance before complete bone repair. Biomaterials with both antibacterial and bone regeneration properties are more promising for bone repair. In the present study, vascular endothelial growth factor (VEGF) was loaded on silk fibroin nanoparticles (SFNPs) and then embedded in silk scaffold containing vancomycin to form a dual drug release system. The chemical and physical properties of the fabricated structure were confirmed by Fourier transform infrared, scanning electron microscopy, and ζ-potential analysis. The size of spherical SFNPs was ∼92 nm. The release kinetics of vancomycin and VEGF showed that ∼99.56% of vancomycin and ∼14% of VEGF were released during 21 and 28 days, respectively. The bioactivity of VEGF was ∼75%. Disk diffusion test confirmed the ability of this drug delivery system against methicillin-resistant Staphylococcus aureus (MRSA). Moreover, expression of the endothelial markers (FLK-1, vWF, and VE-cadherin), alkaline phosphatase, and matrix mineral production were higher in VEGF loaded groups. Taken together, the results indicated that the fabricated codelivery system was able to simultaneously deliver antibiotic and angiogenic factor, which can be considered as a potential candidate for the treatment of contaminated bone injuries.