The many technological advances in the treatment of coronary artery disease since the first attempts by Dotter and Judkins in 1964 to the present day drug eluting stent (DES) have provided clear benefits in terms of improved outcomes for the patient. These improvements, however, have not come without some drawbacks and difficulties, in particular the increase in vessel occlusion experienced with percutaneous transluminal coronary angioplasty (PTCA) and more recently the higher incidence of late thrombosis in patients with DES. This chapter provides the chronology of these developments and by using a risk-benefit-based approach demonstrates how both the safety profile and overall effectiveness of the interventional products have improved. These improvements are such that the provision of device-drug combination products or second generation DES is now considerably safer and more effective than balloon angioplasty or bare metal stents in the treatment of this pernicious disease.

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.

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.

The optimization of CDMA deployed over the legacy analog network is shown to be a complex series of issues and a function of both the intrinsic capacity of CDMA and some practical considerations associated with the incumbent AMPS system. The implications of voice rate, voice quality, deployment strategy and timing on overall network capacity are analyzed together with practical issues of managing the interference between the two networks with use of appropriate guard zones and guard bands etc. The maintenance of call quality, handdown and flawless network operation in the border areas of the dual-mode and analog network are analyzed by including appropriate usage of border and beacon cell sites and CDMA equipment parameters such as cell size. Some of the options available to the network provider in order to balance and optimize the trade-offs between coverage, quality and capacity are analyzed together with how best to proceed in an on-going basis as the growth of both analog and CDMA traffic continues.

To rationally design new synthetic polymers for use in vivo, it is necessary to characterize the surface of the material to understand the interactions that occur when exposed to biological environments. Incorporation of phosphorylcholine (PC) into polymers has been shown to improve biocompatibility by suppressing unfavorable responses which occur on contact with body fluids. Here, polymer blends of [2-(methacryloyloxy)ethyl] phosphorylcholine-co-lauryl methacrylate (MPC-co-LMA(1:6 mole ratio)) and poly(lauryl methacrylate) (PLMA) have been produced with varying ratios of the two components. The surface of the blends when coated onto silver has been characterized using tapping mode atomic force microscopy (TMAFM) and surface plasmon resonance (SPR). Analysis has revealed that the blends formed by the two polymers are immiscible and exhibit surface segregation with nanometer-sized domains being formed throughout the range of the mixtures. The MPC-co-LMA is preferentially expressed at the surface of the blends leading to enhanced protein-resistant properties.

To design new polymers for use in vivo it is necessary to characterize the surface of the material to understand the interactions that occur when it is exposed to biological environments. Incorporation of phosphorylcholine (PC) into polymers has been shown to improve biocompatibility by suppressing unfavorable responses which occur on contact with body fluids. Here, a series of copolymers with varying ratios of the monomers 2-methacryloyloxyethyl phosphorylcholine (MPC) and lauryl (dodecyl)methacrylate (LMA) have been synthesized. The composition of the copolymers were analyzed using nuclear magnetic resonance spectroscopy (NMR), and coatings of these materials characterized using angle-resolved X-ray photoelectron spectroscopy (ARXPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). The interaction of the copolymer coatings with protein was investigated using surface plasmon resonance (SPR), while dynamic contact angle (DCA) was used to monitor the surface hydrophobicity of the copolymers. The combination of the analytical techniques applied to the study of these copolymers has shown that the surfaces are extremely mobile and are able to rearrange depending on the environment in which the polymer is placed. SPR analysis has shown that the plasma protein fibrinogen, known to initiate the clotting cascade, does not adsorb to the surface of the copolymers once they are hydrated.