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Significance Statement
Current commercial polymethylmethacrylate (PMMA) based antibiotics-loaded bone cements exhibit very low drug release as most of the antibiotics are embedded inside the polymerized bone cement. This results in a rapid decrease in antimicrobial activity below the effective therapeutic level within one to several days. To increase the therapeutic window to several weeks for reducing the risk of post-operative joint infection, mesoporous silica nanoparticles (MSN) functional bone cement was developed to enable a sustained release of antibiotics.
Our results show that the novel formulation can be designed to tailor a desired release profile, e.g. up to 70% drug release for several weeks in comparison with commercial bone cement showing 10% or lower drug release and peak concentration only on day one. MSN with uniform nano-porous channels built up effective diffusion nano-networks which enabled the drug molecules to be released sustainably. Moreover, the mechanical properties of bone cements were well preserved in the presence of MSN in formulation even after drug release.
This formulation is expected to deliver the next generation bone cement with tailor-designed antibiotics release profiles and prolonged antibacterial activity. The key commercial advantages to potential bone cement manufacturers and end users are sustained antibiotics release, reduction in standard antibiotics dosage, minimised use of intravenous doses and creating new opportunities to use other benefit ingredient for local targeted delivery. Once commercialized, the socio-economic impact and savings in medical resources and costs are expected to be significant as the risk of post-operative infections can be reduced.
Reference
Shen SC1, Ng WK2, Dong YC2, Ng J2, Tan RB3.
1Institute of Chemical and Engineering Sciences, A*STAR (Agency for Science, Technology and Research), 1 Pesek Road, Jurong Island, Singapore 627833, Singapore. Electronic address: [email protected].
2Institute of Chemical and Engineering Sciences, A*STAR (Agency for Science, Technology and Research), 1 Pesek Road, Jurong Island, Singapore 627833, Singapore.
3Institute of Chemical and Engineering Sciences, A*STAR (Agency for Science, Technology and Research), 1 Pesek Road, Jurong Island, Singapore 627833, Singapore; Department of Chemical and Biomolecular Engineering, The National University of Singapore, 4 Engineering Drive 4, Singapore 117576, Singapore. Electronic address: [email protected].
[/expand]Abstract
To improve antibiotic properties, poly(methyl methacrylate) (PMMA)-based bone cements are formulated with antibiotic and nanostructured materials, such as hydroxyapatite (HAP) nanorods, carbon nanotubes (CNT) and mesoporous silica nanoparticles (MSN) as drug carriers. For nonporous HAP nanorods, the release of gentamicin (GTMC) is not obviously improved when the content of HAP is below 10%; while the high content of HAP shows detrimental to mechanical properties although the release of GTMC can be substantially increased. As a comparison, low content of hollow nanostructured CNT and MSN can enhance drug delivery efficiency. The presence of 5.3% of CNT in formulation can facilitate the release of more than 75% of GTMC in 80 days, however, its mechanical strength is seriously impaired. Among nanostructured drug carriers, antibiotic/MSN formulation can effectively improve drug delivery and exhibit well preserved mechanical properties. The hollow nanostructured materials are believed to build up nano-networks for antibiotic to diffuse from the bone cement matrix to surface and achieve sustained drug release. Based on MSN drug carrier in formulated bone cement, a binary delivery system is also investigated to release GTMC together with other antibiotics.
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