Efficacy of antimicrobial polymer coatings in an animal model of bacterial infection associated with foreign body implants.

OBJECTIVES: To assess support discs, comprising polyethylene terephthalate (PET), coated with different polymer/levofloxacin combinations for antimicrobial activity in an animal model of infection, in order to explore the use of specific polymer coatings incorporating levofloxacin as a means of reducing device-related infections. METHODS: Aliphatic polyester-polyurethanes containing different ratios of poly(lactic acid) diol and poly(caprolactone) diol were prepared, blended with levofloxacin and then used to coat support discs. The in vitro levofloxacin release profiles from these discs were measured in aqueous solution. Mice were surgically implanted with the coated discs placed subcutaneously and infection was initiated by injection of 10(6) cfu of Staphylococcus aureus into the subcutaneous pocket containing the implant. After 5, 10, 20 and 30 days, the discs were removed, and the number of bacteria adhering to the implant and the residual antimicrobial activity of the discs were determined. RESULTS: In vitro, the release of levofloxacin from the coated discs occurred at a constant rate and then reached a plateau at different timepoints, depending on the polymer preparation used. In vivo, none of the discs coated with polymer blends containing levofloxacin was colonized by S. aureus, whereas 94% of the discs coated with polymer alone were infected. All discs coated with levofloxacin-blended polymers displayed residual antimicrobial activity for at least 20 days post-implantation. CONCLUSIONS: Bioerodable polyester-polyurethane polymer coatings containing levofloxacin can prevent bacterial colonization of implants in an intra-operative model of device-related infections.

A biocompatible reverse thermoresponsive polymer for ocular drug delivery.

Age-related macular degeneration (AMD) is a leading cause of vision loss, the treatment of which may require monthly intravitreal injections. This is a burden on patients and health services, and new delivery modalities that reduce injection frequency are required. To that end, we investigated the suitability of a novel reverse thermoresponsive polymer (RTP) as an ocular drug-delivery vehicle. In this work, we detail the structure and synthesis of a novel RTP, and determine drug release curves for two drugs commonly used in the treatment of AMD, bevacizumab and aflibercept. Biocompatibility of the RTP was assessed in vitro in human and rat cell lines and in vivo following intravitreal injection in rats. Bevacizumab demonstrated a more appropriate release profile than aflibercept, with 67% released within 14 days and 78% released in total over a 183-day period. No toxic effects of RTP were seen in human or rat cells in up to 14 days of co-culture with RTP. Following intravitreal injection, intraocular pressure was unaffected by the presence of RTP and no changes in retinal function or structure were observed at 1 week or 1 month post-injection. RTP injection did not cause inflammation, gliosis or apoptosis in the retina. This work demonstrates the potential suitability of the novel RTP as a sustained-release vehicle for ocular drug delivery for anti-neovascular therapies. Optimization of polymer chemistry for optimal drug loading and release is needed.

Biodegradable injectable polyurethanes: synthesis and evaluation for orthopaedic applications.

Biodegradable polyurethanes offer advantages in the design of injectable or preformed scaffolds for tissue engineering and other medical implant applications. We have developed two-part injectable prepolymer systems (prepolymer A and B) consisting of lactic acid and glycolic acid based polyester star polyols, pentaerythritol (PE) and ethyl lysine diisocyanate (ELDI). This study reports on the formulation and properties of a series of cross linked polyurethanes specifically developed for orthopaedic applications. Prepolymer A was based on PE and ELDI. Polyester polyols (prepolymer B) were based on PE and dl-lactic acid (PEDLLA) or PE and glycolic acid (PEGA) with molecular weights 456 and 453, respectively. Several cross linked porous and non-porous polyurethanes were prepared by mixing and curing prepolymers A and B and their mechanical and thermal properties, in vitro (PBS/37 degrees C/pH 7.4) and in vivo (sheep bi-lateral) degradation evaluated. The effect of incorporating beta-tricalcium phosphate (beta-TCP, 5 microns, 10 wt.%) was also investigated. The cured polymers exhibited high compressive strength (100-190 MPa) and modulus (1600-2300 MPa). beta-TCP improved mechanical properties in PEDLLA based polyurethanes and retarded the onset of in vitro and in vivo degradation. Sheep study results demonstrated that the polymers in both injectable and precured forms did not cause any surgical difficulties or any adverse tissue response. Evidence of new bone growth and the gradual degradation of the polymers were observed with increased implant time up to 6 months.

Synthesis of two-component injectable polyurethanes for bone tissue engineering.

The advent of injectable polymer technologies has increased the prospect of developing novel, minimally invasive arthroscopic techniques to treat a wide variety of ailments. In this study, we have synthesised and evaluated a novel polyurethane-based injectable, in situ curable, polymer platform to determine its potential uses as a tissue engineered implant. Films of the polymers were prepared by reacting two pentaerythritol-based prepolymers, and characterised for mechanical and surface properties, and cytocompatibility. This polymer platform displayed mechanical strength and elasticity superior to many injectable bone cements and grafts. Cytotoxicity tests using primary human osteoblasts, revealed positive cell viability and increased proliferation over a period of 7 days in culture. This favourable cell environment was attributed to the hydrophilic nature of the films, as assessed by dynamic contact angle (DCA) analysis of the sample surfaces. The incorporation of beta-TCP was shown to improve mechanical properties, surface wettability, and cell viability and proliferation, compared to the other sample types. SEM/EDX analysis of these surfaces also revealed physicochemical surface heterogeneity in the presence of beta-TCP. Based on preliminary mechanical analysis and cytotoxicity results, these injectable polymers may have a number or potential orthopaedic applications; ranging from bone glues to scaffolds for bone regeneration.

Recent developments in biodegradable synthetic polymers.

This chapter reviews recent developments in biodegradable synthetic polymers focusing on tailoring polymer structures to meet material specification for emerging applications such as tissue engineered products and therapies. Major classes and new families of synthetic polymers are discussed with regard to synthesis, properties and biodegradability, and known degradation modes and products are summarized based on studies reported during the past 10-15 years. Polyesters and their copolymers, polyurethanes, polyphosphazenes, polyanhydrides, polycarbonates, polyesteramides and recently developed injectable polymer systems based on polypropylenefumarates, polyurethanes and acrylate/urethane systems are reviewed. Polyesters such as polyglycolides, polylactides and their copolymers still remain as the major class of synthetic biodegradable polymers with products in clinical use. Although various copolymerization methods have addressed needs of different applications, release of acidic degradation products, processing difficulties and limited range of mechanical properties remains as major disadvantages of this family of polymers. Injectable polymers based on urethane and urethane/acrylate have shown great promise in developing delivery systems for tissue engineered products and therapies.