Biomedical subjects

Andrew L Lewis

Publications and source records attributed to Andrew L Lewis.

26 records · Page 2Linked to original sources

PubMed2004

The effect of phosphorylcholine-coated materials on the inflammatory response and fibrous capsule formation: in vitro and in vivo observations.

Several experiments were performed to compare the in vitro adhesion of human macrophage and granulocyte inflammatory cells to polyethylene terephthalate substrate and the same coated with a phosphorylcholine (PC)-based polymer. The inclusion of various types of serum at different stages in the assay indicated that protein adsorption and passivation of the surface may be responsible for reducing the number of inflammatory cells adhering to the uncoated polyethylene terephthalate controls. In all of the assays performed there was a statistically significant reduction (p < 0.05; analysis of variance) of the number of inflammatory cells adhering to the PC-coated samples, linked to the ability of these surfaces to resist protein adhesion. Implantations of PC-coated stainless steel and high-density polyethylene USP control samples were made in a rabbit intramuscular model. Histological examination of the number of inflammatory cells present around the implant sites 4 weeks postimplantation showed there were 40% less cells associated with the PC-coated samples compared with control, but this was not statistically significant. Fibrous capsule thickness, however, whereas marginally less at 4 weeks, had almost completely regressed for the PC-coated sample at 13 weeks postimplantation and was statistically thinner (p < 0.01; Mann-Whitney U test) than the high-density polyethylene USP control. These findings support the view that low biointeractions observed for PC-based technology in vitro can result in reduced inflammation and foreign body reaction in vivo.

Capsules↗

PubMed2004

Synthesis and characterisation of cationically modified phospholipid polymers.

Phospholipid-like copolymers based on 2-(methacryloyloxyethyl) phosphorylcholine were synthesised using monomer-starved free radical polymerisation methods and incorporating cationic charge in the form of the choline methacrylate monomer in amounts varying from 0 to 30 wt%, together with a 5 wt% silyl cross-linking agent in order to render them water-insoluble once thermally cured. Characterisation using a variety of techniques including nuclear magnetic resonance spectroscopy, high-pressure liquid chromatography and gel permeation chromatography showed the cationic monomer did not interfere with the polymerisation and that the desired amount of charge had been incorporated. Gravimetric and differential scanning calorimetry methods were used to evaluate the water contents of polymer membranes cured at 70 degrees C, which was seen to increase with increasing cation content, producing materials with water contents ranging from 50% to 98%. Surface plasmon resonance indicated that the coatings swelled rapidly in water, the rate and extent of swelling increasing with increasing cation level. Dynamic contact angle showed that coatings of all the polymers possessed a hydrophobic surface when dry in air, characteristic of the alkyl chains expressed at the surface (>100 degrees advancing angle). Rearrangement of the hydrophilic groups to the surface occurred once wet, to produce highly wettable surfaces with a decrease in advancing angle with increasing cation content. Atomic force microscopy showed all polymer films to be smooth with no features in topographical or phase imaging. Mechanical properties of the dry films were also unaffected by the increase in cation content.

Biomimetic Materials↗

PubMed2004

Biological evaluation and drug delivery application of cationically modified phospholipid polymers.

Phospholipid-like polymers based on 2-methacryloyloxyethyl phosphorylcholine containing varying amounts of the cationically charged monomer choline methacrylate (CMA) from 0 to 30 wt% have been prepared. Substrates coated with these materials were shown to bind significantly lower amounts of specific proteins compared to the uncoated control. ELISA assays demonstrated that fibrinogen did not bind appreciably to coatings containing 0-30% CMA, whereas albumin binding was seen to increase significantly as the CMA content of the coating increased. Platelet activation assays, measurement of plasma coagulation time and whole blood contact scanning electron micrography demonstrated that the haemocompatibility of the coatings was shown to be unaffected by the CMA component. The CMA polymer coatings have been shown to absorb/adsorb many different drug compounds covering a wide range of molecular weights and release these in a controlled fashion. The range of cationic polymers assessed can interact with the net negative charge found in many large therapeutic biomolecules, such as DNA fragments used in gene therapy, that may be of interest in the preventative treatment of conditions such as restenosis. Coronary stents coated with 6% or 20% CMA-containing polymers have been shown to load and release this type of genetic material irrespective of molecular weight of the biomolecule. Ex vivo and in vivo studies have shown that these compounds can be delivered to the stented section of the vessel with very low quantities delivered outside the vessel target area.

Absorption↗

PubMed2004

Drug loading and elution from a phosphorylcholine polymer-coated coronary stent does not affect long-term stability of the coating in vivo.

A drug eluting coronary stent was developed for use in preclinical and clinical trial evaluation. The stent was coated with a phosphorylcholine (PC)-based polymer coating containing the cell migration inhibitor batimastat. A pharmacokinetic study was conducted in a rabbit iliac model using (14)C-radiolabeled version of the drug; this showed the drug release to be first order with 94% of it being released within 28 days. Unloaded and drug-loaded stents were implanted in a porcine coronary artery model; a number were explanted at 5 days and scanning electron microscopy was used to show that the presence of the drug did not affect the rate of stent endothelialization. The remainder of the stents were removed after 6 months and the stents carefully removed from the arterial tissue. Fourier-transform infrared (FT-IR) spectroscopy (both attenuated total reflectance and microscopic imaging) was used to show the presence of the PC coating on control unloaded, drug-loaded and explanted stents, providing evidence that the coating was still present. This was further confirmed by use of atomic force microscopy (AFM) amplitude-phase, distance (a-p,d) curves which generated the characteristic traces of the PC coating. Further AFM depth-profiling techniques found that the thicknesses of the PC coatings on an control unloaded stent was 252+/-19 nm, on an control batimastat-loaded stent 906+/-224 nm and on an explanted stent 405+/-224 nm. The increase in thickness after the drug-loading process was a consequence of drug incorporation in the film, and the return to the unloaded dimensions for the explanted sample indicative of elution of the drug from the coating. The drug delivery PC coating was therefore found to be stable following elution of the drug and after 6 months implantation in vivo.

Animals↗

PubMed2002

Phosphorylcholine-coated stents.

Stainless steel stents have been developed to perform their primary purpose of providing sufficient physical support to an artery following percutaneous transluminal coronary angioplasty (PTCA) in order to prevent vessel recoil. Early clinical problems, largely caused by subacute thrombosis (SAT), have been significantly reduced with a new generation of antiplatelet agents. Despite improved pharmacological control of SAT in many patients, the potential for stent occlusion remains a life-threatening problem for those with more complex lesions. One strategy for dealing with this is to improve the hemocompatibility of the stent surface with coatings. A phosphorylcholine (PC)-based stent coating has been designed for this purpose; we describe in detail the evaluation of the device, in vitro, through preclinical and early clinical data. We discuss studies that demonstrate that the PC-coated stent may offer some clinical advantage over uncoated counterparts. The extensive experience with this PC-coated device supports its nonthrombogenic nature, excellent acceptance by arterial tissue, and long-term stability in vivo. These characteristics, together with its ability to load and release a variety of therapeutic agents, also make the device a natural choice of platform for future stent-mediated drug delivery for treating restenosis.

Animals↗

PubMedDate not supplied

The biocompatibility of crosslinkable copolymer coatings containing sulfobetaines and phosphobetaines.

The comparison of copolymers containing sulfobetaine or phosphobetaine moieties for use as potential biocompatible coatings has been investigated. Two statistical copolymers were produced by a free radical polymerisation technique, one based on a sulfobetaine and the other on a phosphobetaine, both with a silyl group component to allow thermal crosslinking after coating. PMMA and glass discs were dip-coated with the polymers and their properties were compared to the uncoated controls. Bacterial adhesion to these coated materials was assessed using Staphylococcus epidermidis, Staphylococcus aureus and Pseudomonas aeruginosa. Human macrophages and granulocytes were used to assess the adhesion and activation of inflammatory cells whilst mouse 3T3 fibroblast cells were used to assess the propensity for the materials to support fibroblast cell adhesion. In all cases the polymer coatings reduced cell adhesion with respect to the base materials. The phosphobetaine-based copolymer coatings were shown to be markedly superior to the sulfobetaine-based copolymer coatings.

3T3 Cells↗

PubMedDate not supplied

Synthesis of biocompatible, stimuli-responsive, physical gels based on ABA triblock copolymers.

ABA triblock copolymers [A = 2-(diisopropylamino)ethyl methacrylate), DPA or 2-(diethylamino)ethyl methacrylate), DEA; B = 2-methacryloyloxyethyl phosphorylcholine, MPC] prepared using atom transfer radical polymerization dissolve in acidic solution but form biocompatible free-standing gels at around neutral pH in moderately concentrated aqueous solution (above approximately 10 w/v % copolymer). Proton NMR studies indicate that physical gelation occurs because the deprotonated outer DPA (or DEA) blocks become hydrophobic, which leads to attractive interactions between the chains: addition of acid leads to immediate dissolution of the micellar gel. Release studies using dipyridamole as a model hydrophobic drug indicate that sustained release profiles can be obtained from these gels under physiologically relevant conditions. More concentrated DPA-MPC-DPA gels give slower release profiles, as expected. At lower pH, fast, triggered release can also be achieved, because gel dissolution occurs under these conditions. Furthermore, the nature of the outer block also plays a role; the more hydrophobic DPA-MPC-DPA triblock gels are formed at lower copolymer concentrations and retain the drug longer than the DEA-MPC-DEA triblock gels.

Biocompatible Materials↗

PubMedDate not supplied

Synthesis and characterization of biocompatible thermo-responsive gelators based on ABA triblock copolymers.

The synthesis of biocompatible, thermo-responsive ABA triblock copolymers in which the outer A blocks comprise poly(N-isopropylacrylamide) and the central B block is poly(2-methacryloyloxyethyl phosphorylcholine) is achieved using atom transfer radical polymerization with a commercially available bifunctional initiator. These novel triblock copolymers are water-soluble in dilute aqueous solution at 20 degrees C and pH 7.4 but form free-standing physical gels at 37 degrees C due to hydrophobic interactions between the poly(N-isopropylacrylamide) blocks. This gelation is reversible, and the gels are believed to contain nanosized micellar domains; this suggests possible applications in drug delivery and tissue engineering.

Acrylic Resins↗