Open AccessDual local drug delivery of vancomycin and farnesol for mitigation of MRSA infection in vivo – a pilot study
Author(s) -
U C Woelfle,
Timothy Briggs,
Sayan Bhattacharyya,
Han Qu,
Navin Sheth,
Christine Knabe,
Paul Ducheyne
Publication year - 2020
Publication title -
european cells and materials
Language(s) - English
Resource type - Journals
eISSN - 1473-2262
DOI - 10.22203/ecm.v040a03
Subject(s) - vancomycin , farnesol , in vivo , drug delivery , microbiology and biotechnology , drug , medicine , staphylococcus aureus , pharmacology , chemistry , biology , bacteria , organic chemistry , genetics
Surgical site infections after orthopaedic surgery using fracture fixation devices or endosseous implants create major surgical challenges with severe adverse effects, such as osteomyelitis. These infections are frequently caused by Staphylococcus aureus, often with high resistance to antibiotics, such as methicillin-resistant Staphylococcus aureus (MRSA). Due to the formation of impenetrable biofilms on implant surfaces, systemic antibiotic treatment has become exceedingly difficult. New solutions are pursued by combining several drugs using a controlled delivery system from specifically engineered implant surfaces. A sol-gel coating on titanium implants was previously developed with 20 wt % vancomycin and 30 wt % farnesol, with suppression of MRSA in vitro. The present study investigated the efficacy of sol-gel film coatings for controlled dual local delivery over 4 weeks utilising a rat infection model. The findings confirmed the viability of this new concept in vivo based on the differences observed between coatings containing vancomycin alone (SGV) and the dual-drug-containing coating with vancomycin and farnesol (SGVF). While both the SGVF and SGV coatings facilitated excellent preservation of the osseous microarchitecture, SGVF coating displayed a slightly higher potency for suppressing MRSA infiltration than SGV, in combination with a lower reactive bone remodelling activity, most likely by disturbing biofilm formation. The next step for advancing the concept of dual-drug delivery from sol-gel coatings to the clinic and confirming the promising effect of the SGVF coatings on reactive bone remodelling and suppressing MRSA infiltration is a study in a larger animal species with longer time points.