Liposomal Antibiotics in Bone Cement
Healthcare and Pharmaceuticals, Life Sciences, Materials
About The Opportunity:
Polymethyl methacrylate bone cement (herein referred to as PMMA) is a self-setting polymer used as a grout to improve the fixation of prosthetic implants in orthopaedics, in particular knee and hip arthroplasty. However, bacterial colonisation, leading to infections and inflammatory responses are known to occur, which can lead to the eventual failure of the implant. To overcome this problem, current bone cement formulations incorporate a certain amount of antibiotics. The antibiotics used are aminoglycosides such as gentamicin sulphate and are loaded into the powder component of the cement at high concentrations, roughly 4% w/w or 1g per 40g of PMMA bone cement. These high concentrations can lead to increased costs and also weakening of the cement, reducing mechanical and fatigue properties.
Although large quantities of the antibiotic are introduced into the cement, only fractions of it are released into the surrounding tissue (0-10%) and this occurs within the first 6 hours of implantation. This is due to the diffusion of antibiotics from the surface of the cement only, leaving the bulk of the antibiotics deeper in the cement mantle. Inventors at Cardiff University have developed a novel composition of bone cement, incorporating a liposomal drug delivery system into to improve the dispersion of therapeutic agents, release characteristics and antibacterial and antimicrobial properties without compromising mechanical strength and fatigue properties.
Lipids are composed of a hydrophilic polar head group and two hydrophobic fatty acid chains linked by a glycerol bridge. When suspended in water these lipids form bilayers which rearrange themselves into spherical vesicles. Within these vesicles, a combination of antibiotics or therapeutic agents can be encapsulated for better controlled release rates. Certain lipid head groups have also been shown to enhance calcification and therefore there is a possibility for promoting better bone growth in bone cements with the potential of promoting a self-healing mechanism.
- This system is stable throughout a range of temperatures (4-80°C) and has been shown to survive the exothermic process of setting bone cement.
- When this aqueous solution is incorporated into the liquid component of the bone cement and thus the polymer matrix, a better overall dispersion of the therapeutic agent is observed.
- Therefore this invention improves the dispersion of the therapeutic agent within the bone cement matrix and as a result of this, improves the release characteristics.
- No reduction in mechanical and fatigue properties
- Improved therapeutic index by altering pharmacokinetics and pharmacodynamics
- Encapsulated gentamicin was also found to have longer half-lives than free gentamicin in in vivo studies.
A UK provisional filing has been made in respect of this technology