title: Sustainable Release of Vancomycin from Silk Fibroin Nanoparticles for Treating Severe Bone Infection in Rat Tibia Osteomyelitis Model.
abstract: The successful treatment of bone infections is a major challenge in the field of orthopedics. There are some common methods for treating bone infections, including systemic antibiotic administration, local nondegradable drug vehicles, and surgical debridement, and each of these approaches has advantages and disadvantages. In the present study, the antibiotic vancomycin (VANCO) was loaded in silk fibroin nanoparticles (SFNPs) and the complexes were then entrapped in silk scaffolds to form sustained drug delivery systems. The release kinetics of VANCO from SFNPs alone and when the SFNPs were entrapped in silk scaffolds were assessed at two different pH values, 4.5 and 7.4, that affected the release profiles of VANCO. Disk diffusion tests performed with pathogens causing osteomyelitis methicillin-resistant Staphylococcus aureus (MRSA) showed antibacterial activity of the released drug at two different pH values. Additionally, injection of 8 × 106CFU MRSA in rat's tibia induced severe osteomyelitis disease. Radiographic and histopathological analyses were performed to evaluate the effectiveness of treatment after 6 weeks. The VANCO-loaded silk fibroin nanoparticles entrapped in scaffolds reduced bone infections at the defected site with better outcomes than the other treatment groups. In conclusion, the delivery system with good biocompatibility and sustained release properties would be appropriate for further study in the context of osteomyelitis disease.
authors.affiliation: School of Chemical Engineering, Collage of Engineering, University of Tehran , P.O. Box 11155-4563, Tehran 1417466191, Iran.
authors.forename: Negar
authors.initials: N
authors.lastname: Hassani Besheli
authors.affiliation: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences , P.O. Box 14155-6451, Tehran 1417613151, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Mottaghitalab
authors.affiliation: Materials Science & Engineering Department, Sharif University of Technology , P.O. Box 11365-9466, Tehran 145888-9694, Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Eslami
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Science Research Center, Tehran University of Medical Sciences , P.O. Box 14155-6451, Tehran 1417613151, Iran.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Gholami
authors.affiliation: 3Bs Research Group, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho , AvePark, Barco, Guimaraes 4805-017, Portugal.
authors.forename: Subhas C
authors.initials: SC
authors.lastname: Kundu
authors.affiliation: Department of Biomedical Engineering, Tufts University , 4 Colby Street, Medford, Massachusetts 02155, United States.
authors.forename: David L
authors.identifier: http://orcid.org/0000-0002-9245-7774
authors.initials: DL
authors.lastname: Kaplan
authors.affiliation: National Cell Bank of Iran, Pasteur Institute of Iran , P.O. Box 1316943551, Tehran 1316943551, Iran.
authors.forename: Mehdi
authors.identifier: http://orcid.org/0000-0001-7023-2905
authors.initials: M
authors.lastname: Farokhi
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents; D005349:Fibroins; D055624:Methicillin-Resistant Staphylococcus aureus; D053758:Nanoparticles; D010019:Osteomyelitis; D051381:Rats; D013203:Staphylococcal Infections; D013977:Tibia; D014640:Vancomycin
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D005349:Fibroins
keywords: bone infection; nanoparticle; osteomyelitis; scaffold; silk; vancomycin