Laurence Meagher

The isoelectric points of sapphire crystals and alpha-alumina powder

Abstract Streaming potential measurements and atomic force microscropy (AFM) were used to determine the zeta potentials, diffuse layer potentials and isoelectric points (ieps) of alpha alumina sapphire single crystals for four different crystallographic orientations: c-plane, 0001 ; a-plane, 11 2 0 ; m-plane, 10 1 0 ; and r-plane, 1 1 02 . Both types of measurements indicated that the iep of the sapphire crystals was between about pH 5.0 and 6.0 for all crystals investigated. Unfortunately the techniques utilized could not conclusively differentiate any subtle differences in iep between the four orientations studied. The iep of alpha alumina powder was found to be pH 9.4. The difference in the ieps of the two different types of alpha alumina (single crystal and powder) is attributed to the presence of different types of surface hydroxyl groups on the two different types of surfaces. Powder is likely to have a greater fraction of singly coordinated surface hydroxyl groups (that have a high p K a ), while sapphire single crystals are more likely to have most surface hydroxyls multiply coordinated (which have a low p K a ).

Guanylated Polymethacrylates: A Class of Potent Antimicrobial Polymers with Low Hemolytic Activity

We have synthesized a series of copolymers containing both positively charged (amine, guanidine) and hydrophobic side chains (amphiphilic antimicrobial peptide mimics). To investigate the structure-activity relationships of these polymers, low polydispersity polymethacrylates of varying but uniform molecular weight and composition were synthesized, using a reversible addition-fragmentation chain transfer (RAFT) approach. In a facile second reaction, pendant amine groups were converted to guanidines, allowing for direct comparison of cation structure on activity and toxicity. The guanidine copolymers were much more active against Staphylococcus epidermidis and Candida albicans compared to the amine analogues. Activity against Staphylococcus epidermidis in the presence of fetal bovine serum was only maintained for guanidine copolymers. Selectivity for bacterial over mammalian cells was assessed using hemolytic and hemagglutination toxicity assays. Guanidine copolymers of low to moderate molecular weight and hydrophobicity had high antimicrobial activity with low toxicity. Optimum properties appear to be a balance between charge density, hydrophobic character, and polymer chain length. In conclusion, a suite of guanidine copolymers has been identified that represent a new class of antimicrobial polymers with high potency and low toxicity.

Interactions of lens care with silicone hydrogel lenses and effect on comfort.

Purpose. The purpose of this study was to investigate the effect of lens care products on short-term subjective and physiological performance silicone hydrogel lenses. Methods. Ten subjects wore either lotrafilcon B or galyfilcon A silicone hydrogel contact lenses soaked in a lens care product containing either Polyquad/Aldox or PHMB or control lenses inserted directly from the pack. Subjects wore the lenses for 6 h. Ocular comfort (graded on a 1 to 10 scale) and ocular physiology were assessed. Unworn but soaked lenses were analyzed for metrological changes, release of excipients into phosphate buffered saline, and changes to their surface chemical composition. Results. None of the lens metrology measures or clinically observed conjunctival or limbal redness changed. Corneal staining was significantly (p < 0.008) raised, albeit to low levels, after 6 h wear for either lens type when soaked in the PHMB solution compared with the control lens (lotrafilcon B 0.4 to 0.9 ± 0.7 to 0.4 vs. 0.1 to 0.4 ± 0.3 to 0.5; galyfilcon A 0.2 to 0.3 ± 0.2 to 0.4 vs. 0.0 ± 0.0). For lotrafilcon B lenses, there were decreases in comfort (p = 0.002), increases in burning/stinging (p = 0.002) after 1 h of wear, and increases in lens awareness on lens insertion (p = 0.0001) when soaked in PHMB. However, lotrafilcon B lenses soaked in Polyquad/Aldox showed increases in burning/stinging after 1 and 6 h (p < 0.008) of lens wear. For galyfilcon A lenses, most significant (p ≤ 0.002) changes to symptomatology occurred after soaking in Polyquad/Aldox solution. More PHMB was released from lotrafilcon B lenses, and more MPDS material was released from galyfilcon A lenses. The surface of galyfilcon A lenses changed but irrespective of lens solution type, whereas the changes to the lens surface was dependent on solution type for lotrafilcon B lenses. Conclusions. Lens care products can change corneal staining and comfort responses during wear. These changes may be associated with release of material soaked into lenses or changes to the lens surface composition.

Clinical observations of biofouling on PEO coated silicone hydrogel contact lenses

Silicone hydrogel contact lenses, which have been a major advance in the field of vision correction, require surface modification or coatings for comfort and biocompatibility. While current coatings show adequate clinical performance, advanced coatings may improve the biocompatibility of contact lenses further by reducing biofouling and related adverse clinical events. Here, we have produced coatings on Lotrafilcon A contact lenses by deposition of a thin film of allylamine plasma polymer (ALAPP) as a reactive interlayer for the high density grafting of poly(ethylene oxide) dialdehyde (PEO(ALD)(2)), which had previously shown complete resistance to protein adsorption in vitro. The performance of these contact lenses was evaluated in a controlled clinical study over 6h using Focus Night and Day (also known as Air Optix Night & Day) contact lenses as control lenses. Surface modified lenses were characterised by X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) before and after wear. Clinical data showed a high level of biocompatibility of the PEO coated lenses equivalent to control lenses. Surface analysis of worn contact lenses demonstrated that the high density PEO coating is effective in reducing biofouling in vivo compared to control lenses, however small amounts of protein deposits were still detected on all worn contact lenses. This study highlights that elimination of biofouling in vivo can be much more demanding than in vitro and discusses issues that are important for the analysis of worn contact lenses as well as the design of improved contact lenses.

Thermally cross-linked PNVP films as antifouling coatings for biomedical applications.

Protein repellent coatings are widely applied to biomedical devices in order to reduce the nonspecific adhesion of plasma proteins, which can lead to failure of the device. Poly(N-vinylpyrrolidone) (PNVP) is a neutral, hydrophilic polymer with outstanding antifouling properties often used in these applications. In this paper, we characterize for the first time a cross-linking mechanism that spontaneously occurs in PNVP films upon thermal annealing. The degree of cross-linking of PNVP films and their solubility in water can be tailored by controlling the annealing, with no need for additional chemical treatment or irradiation. The physicochemical properties of the cross-linked films were investigated by X-ray photoelectron spectroscopy, infrared spectroscopy, neutron and X-ray reflectometry, ellipsometry, and atomic force microscopy, and a mechanism for the thermally induced cross-linking based on radical formation was proposed. The treated films are insoluble in water and robust upon immersion in harsh acid environment, and maintain the excellent protein-repellent properties of unmodified PNVP, as demonstrated by testing fibrinogen and immunoglobulin G adsorption with a quartz crystal microbalance. Thermal cross-linking of PNVP films could be exploited in a wide range of biotechnological applications to give antifouling properties to objects of any size, essentially making this an alternative to high-tech surface modification techniques.

Biomedical applications of polymers derived by reversible addition – fragmentation chain-transfer (RAFT)

RAFT- mediated polymerization, providing control over polymer length and architecture as well as facilitating post polymerization modification of end groups, has been applied to virtually every facet of biomedical materials research. RAFT polymers have seen particularly extensive use in drug delivery research. Facile generation of functional and telechelic polymers permits straightforward conjugation to many therapeutic compounds while synthesis of amphiphilic block copolymers via RAFT allows for the generation of self-assembled structures capable of carrying therapeutic payloads. With the large and growing body of literature employing RAFT polymers as drug delivery aids and vehicles, concern over the potential toxicity of RAFT derived polymers has been raised. While literature exploring this complication is relatively limited, the emerging consensus may be summed up in three parts: toxicity of polymers generated with dithiobenzoate RAFT agents is observed at high concentrations but not with polymers generated with trithiocarbonate RAFT agents; even for polymers generated with dithiobenzoate RAFT agents, most reported applications call for concentrations well below the toxicity threshold; and RAFT end-groups may be easily removed via any of a variety of techniques that leave the polymer with no intrinsic toxicity attributable to the mechanism of polymerization. The low toxicity of RAFT-derived polymers and the ability to remove end groups via straightforward and scalable processes make RAFT technology a valuable tool for practically any application in which a polymer of defined molecular weight and architecture is desired.

Immobilized liposome layers for drug delivery applications: inhibition of angiogenesis.

Liposomes were immobilized onto the surface of perfluorinated polymer tape samples and tissue culture polystyrene well-plates using a multilayer immobilization strategy. In the first step, a thin interfacial bonding layer with surface aldehyde groups was deposited from a glow discharge struck in acetaldehyde vapour. Polyethylenimine was then covalently bound onto the aldehyde groups by reductive amination, followed by covalent binding of NHS-PEG-biotin molecules onto the surface amine groups by carbodiimide chemistry. Next, NeutrAvidin protein molecules were bound onto the PEG-biotin layer. Finally, liposomes containing PEG-biotinylated lipids were docked onto the remaining binding sites of the surface-immobilized NeutrAvidin molecules. AFM was used to image surface-bound liposomes and revealed a density well below close packing. The release characteristics of the surface-bound liposomes were measured by the fluorescence intensity changes of carboxyfluorescein upon release. Liposomes filled with sodium orthovanadate were surface immobilized and used in two in vitro angiogenesis assays. Marked differences compared to various control samples were observed, demonstrating the utility of drug-filled, surface-bound liposomes for evoking localized, controlled biological host responses proximal to an implanted biomedical device.

RAFT-derived antimicrobial polymethacrylates: elucidating the impact of end-groups on activity and cytotoxicity

Antimicrobial polymers as mimics of natural antimicrobial peptides are emerging as an alternative to classic antibiotics due to their potency, selectivity and lower susceptibility to resistance. The key chemical aspects necessary to confer high activity and selectivity to the polymer chain composition are largely known. However, little attention has been paid to how end-groups affect the overall biological activity. Here we report the use of RAFT polymerization to obtain eight well-defined cationic methacrylate polymers which bear either amine (PA1–4) or guanidine (PG1–4) pendant groups, while systematically varying the R- and Z-RAFT end-groups. These polymers were assessed in haemotoxicity assays as well as antimicrobial testing against clinically relevant pathogens; such as a vigorously biofilm forming strain of Staphylococcus epidermidis (S. epidermidis) and a vancomycin and methicillin resistant strain of Staphylococcus aureus (VISA) as well as the opportunistic fungus Candida albicans (C. albicans). The R-group was found to dominate the measured toxicity of polymers. Replacement of the anionic cyanovaleric acid R-group (PA1) with the neutral isobutyronitrile (PA3) led to over a 20 fold increase in the haemolytic activity of the polymers. The Z-group, however, was found to have more influence on the antimicrobial activity of the polymers against both VISA and C. albicans, whereby polymers with a long, lipophilic dodecylsulfanyl Z-group (PA1) were found to be more potent than those with either an ethylsulfanyl or no ZCS2-group. These results indicate that chemical control over the end-groups is a key element for achieving the desired high biological activity and selectivity, particularly when low molecular weights are required for maximum antibacterial activity.

Surface modification of electrospun fibres for biomedical applications: A focus on radical polymerization methods.

The development of electrospun ultrafine fibres from biodegradable and biocompatible polymers has created exciting opportunities for biomedical applications. Fibre meshes with high surface area, suitable porosity and stiffness have been produced. Despite desirable structural and topographical properties, for most synthetic and some naturally occurring materials, the nature of the fibre surface chemistry has inhibited development. Hydrophobicity, undesirable non-specific protein adsorption and bacterial attachment and growth, coupled with a lack of surface functionality in many cases and an incomplete understanding of the myriad of interactions between cells and extracellular matrix (ECM) proteins have impeded the application of these systems. Chemical and physical treatments have been applied in order to modify or control the surface properties of electrospun fibres, with some success. Chemical modification using controlled radical polymerization, referred to here as reversible-deactivation radical polymerization (RDRP), has successfully introduced advanced surface functionality in some fibre systems. Atom transfer radical polymerization (ATRP) and reversible addition fragmentation chain transfer (RAFT) are the most widely investigated techniques. This review analyses the practical applications of electrospinning for the fabrication of high quality ultrafine fibres and evaluates the techniques available for the surface modification of electrospun ultrafine fibres and includes a detailed focus on RDRP approaches.

Interfacial properties and protein resistance of nano-scale polysaccharide coatings

For many applications, it is essential to be able to control the interface between devices and the biological environment by nanoscale control of the composition of the surface chemistry and the surface topography. Application of molecular thickness coatings of biologically active macromolecules provides predictable interfacial control over interactions with biological media. The covalent surface immobilization of polysaccharides, proteins and synthetic oligopeptides can be achieved via nanometres thick, interfacial bonding layers deposited by gas plasma methods, and the multi-step coating schemes are verified by XPS analyses. Interactions between biomolecular coatings and biological fluids are studied by MALDI mass spectrometry and ELISA assays. Using a colloid-modified AFM tip, quantitative measurement of interfacial forces is achieved. Comparison with theoretical predictions allows elucidation of the key interfacial forces that operate between surfaces and approaching bio-macromolecules. In this way, it is possible to unravel the fundamental information required for the guided design and optimization of biologically active nanoscale coatings that confer predictable properties to synthetic carriers used for the fabrication of bio-diagnostics and biomedical devices. By studying the relationships between interfacial forces and the adsorption of proteins, we have established the key properties that make specific polysaccharide coatings resistant to the adsorption of proteins, which is applicable to biomaterial, biosensor and biochip research.