Atom transfer radical polymerisation - towards the synthesis of a fully-functional photorefractive polymer

Atom transfer radical polymerisation (ATRP) of styrene in xylene solution initiated with 1-phenylethyl bromide and mediated by CuBr/N-propyl-2- pyridinemethanimine catalyst complex was studied. The polymerisation was ill-controlled, yielding polymers with broad molecular weight distributions and values of number average molecular weight considerably higher than the theoretical values calculated from 100% initiator efficiency. The degree of control afforded over the polymerisation was enhanced by use of a more soluble catalyst complex, CuBr/N-octyl-2-pyridinemethanimine. Furthermore, the use of a more polar solvent, diglyme, generated a homogeneous catalyst complex that facilitated the production of polymers having narrow molecular weight distributions (1.10 < PDi < 1.20). The kinetics of the atom transfer radical polymerisation of methyl methacrylate at 90°C in diglyme solution initiated with ethyl-2-bromoisobutyrate and mediated by CuBr/N-octyl-2-pyridinemethanimine was studied and the orders of the reaction were established. The effect on the rate of polymerisation of the ratio of CuBr:N-octyl-2-pyridinemethanimine was also determined. The temperature dependencies of the rate of polymerisation of methyl methacrylate in diglyme solution and xylene solution were studied, and were found to be non-linear and dependent upon the polarity of the solvent. The use of highly polar aprotic solvents, such as N,N-dimethylformamide and dimethylsulphoxide, was found to be detrimental to the degree of control afforded over the polymerisation of methyl methacrylate. This was circumvented by use of a 5-fold excess, over that conventionally used, of catalyst complex. The atom transfer radical polymerisation of (4-nitrophenyl)-[3-[N-[2- (methacryloyloxy)ethyl]carbazolyl]]diazene in dimethyl sulphoxide solution was studied. Although homopolymerisation yielded only oligomers, copolymerisation of this monomer with methyl methacrylate was found to be readily achievable. Keywords: ATRP, Styrene; Methyl methacrylate; Polar solvents; Fully-functional photorefractive polymer. 2

Chemical and physical methods of enhancing the percutaneous absorption of antimicrobial agents

Contrary to previously held beliefs, it is now known that bacteria exist not only on the surface of the skin but they are also distributed at varying depths beneath the skin surface. Hence, in order to sterilise the skin, antimicrobial agents are required to penetrate across the skin and eliminate the bacteria residing at all depths. Chlorhexidine is an antimicrobial agent with the widest use for skin sterilisation. However, due to its poor permeation rate across the skin, sterilisation of the skin cannot be achieved and, therefore, the remaining bacteria can act as a source of infection during an operation or insertion of catheters. The underlying theme of this study is to enhance the permeation of this antimicrobial agent in the skin by employing chemical (enhancers and supersaturated systems) or physical (iontophoresis) techniques. The hydrochloride salt of chlorhexidine (CHX), a poorly soluble salt, was used throughout this study. The effect of ionisation on in vitro permeation rate across the excised human epidennis was investigated using Franz-type diffusion cells. Saturated solutions of CHX were used as donor and the variable studied was vehicle pH. Permeation rate was increased with increasing vehicle pH. The pH effect was not related to the level of ionisation of the drug. The effect of donor vehicle was also studied using saturated solutions of CHX in 10% and 20% ethanol as the donor solutions. Permeation of CHX was enhanced by increasing the concentration of ethanol which could be due to the higher concentration of CHX in the donor phase and the effect of ethanol itself on the membrane. The interplay between drug diffusion and enhancer pretreatment of the epidennis was studied. Pretreatment of the membrane with 10% Azone/PG demonstrated the highest diffusion rate followed by 10% olcic acid/PG pretreatment compared to other pretreatment regimens (ethanol, dimethyl sulfoxide (DMSO), propylene glycol (PG), sodium dodecyl sulphate (SDS) and dodecyl trimethyl ammonium bromide (DT AB). Differential Scanning Calorimetry (DSC) was also employed to study the mode of action of these enhancers. The potential of supersaturated solutions in enhancing percutaneous absorption of CHX was investigated. Various anti-nucleating polymers were screened in order to establish the most effective agent. Polyvinylpyrrolidone (PVP, K30) was found to be a better candidate than its lower molecular weight counterpart (K25) and hydroxypropyl methyleellulose (HPMC). The permeation studies showed an increase in diffusion rate by increasing the degree of saturation. Iontophoresis is a physical means of transdemal drug delivery enhancement that causes an increased penetration of molecules into or through the skin by the application of an electric field. This technique was employed in conjunction with chemical enhancers to assess the effect on CHX permeation across the human epidermis. An improved transport of CHX, which was pH dependant was observed upon application of the current. Combined use of iontophoresis and chemical enhancers further increased the CHX transport indicating a synergistic effect. Pretreatment of the membrane with 10% Azone/PG demonstrated the greatest effect.

International flavours

It is an Olympic year and we have just witnessed the fantastic games hosted by Rio de Janeiro. Well done to team USA for winning the most medals overall but also well done to so many other nations and individuals who performed so well or were ambassadors in other ways. Teenage swimmer Yusra Mardini who swam for the refugee team and South Africa's Wayde van Niekerk who broke the longstanding 400 m record of Michael Johnson that has stood since 1999. Of course, we must mention sprinter Usain Bolt and swimmer Michael Phelps, who have now transcended superstar status and entered a new level of icon. My personal highlight was the sportsmanship witnessed in the 5000 m when American Abbey D’Agostino was accidentally felled by New Zealand runner Nikki Hamblin. D’Agostino helped Hamblin back to her feet but slumped to the track after realising her own injury. Hamblin helped her up and stayed with her so that both completed the race. The International Olympic Committee has awarded both with the prestigious Pierre de Coubertin award, also known as the International Fair Play Trophy. Fair play is of paramount importance in publishing in peer-reviewed papers. At CLAE we try and maintain, as do other journals, this by ensuring double blind peer review and allowing authors to select the most appropriate handling editor for their submission. Our handling editors are placed across the world (2 in Europe, 1 in the Americas, 1 in Australia and 1 in Asia) and part of their role is to encourage submissions from their region. Over the last decade we certainly have seen more and more papers from places that haven’t previously published in CLAE. In this issue of CLAE we have a true international blend of papers. We have papers from authors from the UK, USA, Iran, Jordan, France, Poland, Turkey, Nigeria, France, Spain and Brazil. I think it's a testament to the continued success of the journal that we are attracting new writers from so many parts of the world and retain papers from more established authors and research centres. We do continue to attract many weaker papers that are rejected early in the review process. Often these will be unexceptional case reports or papers describing a surgical technique. Case reports are published but only those that offer something original and especially those with interesting photographs. In this issue you will see Professor James Wolffsohn (UK) has an interesting paper around a lot of the focus of his recent research activity into clinical evaluation of methods of correcting presbyopia. In this paper he highlights predictors to aid success of presbyopic contact lenses. If you have been involved in any clinical work or research in the field of dry eye disease then you will know well the CLDEQ (Contact Lens Dry Eye Questionnaire) devised by Robin Chalmers and her colleagues (USA). This issue of CLAE details the latest research using the CLDEQ-8 (the 8 item version of the CLDEQ). The Shahroud Eye Cohort Study has produced many papers already and in this issue we see Fotouhi Akbar (Iran) looking at changes in central and peripheral corneal thickness over a five year period. These days we use a lot of new instrumentation, such as optical low-coherence reflectometry. In this issue Emre Güler (Turkey) compares that to a new optical biometry unit. Dry eye is more common and in this issue we see a study by Oluyemi Fasina (Nigeria) to investigate the disease in adults in South-West Nigeria. The TearLab™ is now commonly used to investigate osmolarity and Dorota Szczesna-Iskander (Poland) looks at measurement variability of this device. Following the theme of dry eyes and tear testing Renaud Laballe (France) looks at the use of scleral lenses as a reservoir-based ocular therapeutic system. In this issue we have a couple of papers looking at different aspects of keratoconus. Magdalena Popiela (UK) looks at demographics of older keratoconic patients in Wales, Faik Orucoglu (Turkey) reports a novel scoring system for distinguishing keratoconus from normal eyes, Gonzalo Carracedo (Spain) reports the effect of rigid gas permeable lens wear on dry eye in keratoconus and Hatice Nur Colak (Turkey) compares topographic and aberrations in keratoconus. Other interesting papers you will find are Mera Haddad (Jordan) investigates contact lens prescribing in Jordan, Camilla Fraga Amaral (Brazil) offers a report on the use of ocular prosthetics, Naveed Ahmed Khan (Malaysia) reports of the use of dimethyl sulfoxide in contact lens disinfectant and Michael Killpartrick (UK) offers a short piece with some useful advice on contamination risk factors that may occur from the posterior surface of disposable lenses. So for this issue I would say that the Gold Medal for biggest contribution in terms of papers has to go to Turkey. I could have awarded it to the UK too, but Turkey has three full papers and the UK has two plus one short communication. Turkey is also one of the countries that has shown the largest increase in submissions over the last decade. Finally, welcome aboard to our newest Editorial Board Member Nicole Carnt from Australia. Nicole has been an active researcher for many years and acted as a reviewer for CLAE many times in the past. We look forward to working with you.