Use of in vitro and haptic assessments in the characterisation of surface lubricity

Lubricity is a key property of hydrophilic-coated urinary catheter surfaces. In vitro tests are commonly employed for evaluation of surface properties in the development of novel catheter coating technologies, however, their value in predicting the more subjective feeling of lubricity requires validation. We herein perform a range of in vitro assessments and human organoleptic studies to characterise surface properties of developmental hydrophilic coating formulations, including water wettability, coefficient of friction, dry-out kinetics and lubricity. Significant reductions of up to 40% in the contact angles and coefficient of friction values of the novel coating formulations in comparison to the control poly(vinyl pyrrolidone)-coated surfaces were demonstrated during quantitative laboratory assessments. In contrast, no significant differences in the more subjective feeling of lubricity between the novel formulations and the control-coated surfaces were observed when formulations were haptically assessed by the techniques described herein. This study, importantly, highlights the need for optimisation of in vitro and human haptic assessments to more reliably predict patient preferences

Photochemically controlled drug dosing from a polymeric scaffold

Purpose To develop the first photoactive biomaterial coating capable of controlled drug dosing via inclusion of synthesised drug-3,5-dimethoxybenzoin (DMB) conjugates in a poly(2-methyoxyethyl acrylate) (pMEA) scaffold. Methods Flurbiprofen- and naproxen-DMB conjugates were prepared via esterification and characterised via NMR spectroscopy and mass spectrometry following chromatographic purification. Conjugate photolysis was investigated in acetonitrile solution and within the pMEA matrix following exposure to low-power 365 nm irradiation. Photo-liberation of drug from pMEA into phosphate buffered saline was monitored using UV-vis spectroscopy. Results The synthetic procedures yielded the desired drug conjugates with full supporting characterisation. Drug regeneration through photolysis of the synthesised conjugates was successful in both acetonitrile solution and within the pMEA scaffold upon UV irradiation. Conjugates were retained within the pMEA scaffold with exclusive drug liberation following irradiation and increased drug dose with increasing exposure. Multi-dosing capacity was demonstrated though the ability of successive irradiation periods to generate further bursts of drug. Conclusion This study demonstrates the first application of photochemically controlled drug release from a biomaterial coating and the feasibility of using pMEA as a scaffold for housing the photoactive drug-DMB conjugates

Hydrogel-forming microneedle arrays made from light-responsive materials for on-demand transdermal drug delivery

We describe, for the first time, stimuli-responsive hydrogel-forming microneedle (MN) arrays that enable delivery of a clinically-relevant model drug (ibuprofen) upon application of light. MN arrays were prepared using a polymer prepared from 2-hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethacrylate (EGDMA) by micromolding. The obtained MN arrays showed good mechanical properties. The system was loaded with up to 5% (w/w) ibuprofen included in a light-responsive 3,5-dimethoxybenzoin conjugate. Raman spectroscopy confirmed the presence of the conjugate inside the polymeric MN matrix. In vitro, this system was able to deliver up to three doses of 50 mg of ibuprofen upon application of an optical trigger over a prolonged period of time (up to 160 hours). This makes the system appealing as a controlled release device for prolonged periods of time. We believe that this technology has potential for use in “on-demand” delivery of a wide range of drugs in a variety of applications relevant to enhanced patient care

Systematic optimization of poly(vinyl chloride) surface modification with an aromatic thiol

Abstract The efficient covalent functionalization of poly(vinyl chloride) (PVC), which is widely used in medical device manufacture, allows an array of potential property-enhancing surface modifications to be made. To demonstrate a general method of functionalization via substituted (functional) thiols, we describe a systematic approach to the optimization of PVC surface modification by nucleophilic substitution with 4-aminothiophenol through control of reaction conditions: solvent composition, sonication, reaction time and presence of base and/or phase transfer catalyst (PTC). Efficient thiol attachment was confirmed using solid-state NMR and Raman spectroscopies, and the extent of surface modification was quantified using ATR-FTIR spectroscopy. Sonicated samples exhibited a lower degree of modification than their statically immersed counterparts (21.7 vs 99.6 μg cm-3), and mechanical integrity was compromised. In DMSO/H2O systems with a PTC, resultant degrees of PVC surface modification were up to 12.5% higher when caesium carbonate was employed as the base than in corresponding systems with potassium carbonate

A four-helix bundle stores copper for methane oxidation

Methane-oxidising bacteria (methanotrophs) require large quantities of copper for the membrane-bound (particulate) methane monooxygenase (pMMO). Certain methanotrophs are also able to switch to using the iron-containing soluble MMO (sMMO) to catalyse methane oxidation, with this switchover regulated by copper. MMOs are Nature’s primary biological mechanism for suppressing atmospheric levels of methane, a potent greenhouse gas. Furthermore, methanotrophs and MMOs have enormous potential in bioremediation and for biotransformations producing bulk and fine chemicals, and in bioenergy, particularly considering increased methane availability from renewable sources and hydraulic fracturing of shale rock. We have discovered and characterised a novel copper storage protein (Csp1) from the methanotroph Methylosinus trichosporium OB3b that is exported from the cytosol, and stores copper for pMMO. Csp1 is a tetramer of 4-helix bundles with each monomer binding up to 13 Cu(I) ions in a previously unseen manner via mainly Cys residues that point into the core of the bundle. Csp1 is the first example of a protein that stores a metal within an established protein-folding motif. This work provides a detailed insight into how methanotrophs accumulate copper for the oxidation of methane. Understanding this process is essential if the wide-ranging biotechnological applications of methanotrophs are to be realised. Cytosolic homologues of Csp1 are present in diverse bacteria thus challenging the dogma that such organisms do not use copper in this location