Controlled drug release from hydrogels for contact lenses: drug partitioning and diffusion

Optimization of drug delivery from drug loaded contact lenses assumes understanding the drug transport mechanisms through hydrogels which relies on the knowledge of drug partition and diffusion coefficients. We chose, as model systems, two materials used in contact lens, a poly-hydroxyethylmethacrylate (pHEMA) based hydrogel and a silicone based hydrogel, and three drugs with different sizes and charges: chlorhexidine, levofloxacin and diclofenac. Equilibrium partition coefficients were determined at different ionic strength and pH, using water (pH 5.6) and PBS (pH 7.4). The measured partition coefficients were related with the polymer volume fraction in the hydrogel, through the introduction of an enhancement factor following the approach developed by the group of C. J. Radke (Kotsmar et al., 2012; Liu et al., 2013). This factor may be decomposed in the product of three other factors EHS, Eel and Ead which account for, respectively, hard-sphere size exclusion, electrostatic interactions, and specific solute adsorption. While EHS and Eel are close to 1, Ead > > 1 in all cases suggesting strong specific interactions between the drugs and the hydrogels. Adsorption was maximal for chlorhexidine on the silicone based hydrogel, in water, due to strong hydrogen bonding. The effective diffusion coefficients, De, were determined from the drug release profiles. Estimations of diffusion coefficients of the non-adsorbed solutes D = De × Ead allowed comparison with theories for solute diffusion in the absence of specific interaction with the polymeric membrane.info:eu-repo/semantics/publishedVersio

FIELDS, WORLDS AND FIGURATIONS: USING ELIAS TO REVISIT DEPTH CONCEPTUAL IMAGERY AND EMANCIPATORY CRITIQUE

We centrally explore the significance of conceptual imagery, particularly ideas of ‘depth’ and its relationship to ideals of critique, emancipatory action, and conceptions of social structure and action. We consider how depth imagery is invoked in critiques of sociological thinkers understood to employ ‘flat’ social ontologies. We develop a three-way comparison between Pierre Bourdieu’s ‘field,’ Howard Becker’s ‘world,’ and Norbert Elias’s ‘figuration’ to argue that not only is the ‘flatness’ charge unwarranted in the case of Becker’s and Elias’s ontologies, but the axioms upon which it is made are static, substantialist, and reductively mechanistic. Drawing on the work of Elias, we consider the merits of alternative more dynamically oriented conceptual imagery, reflecting upon its implications for how we might revisit the ‘politics’ of figurational sociology and understandings of emancipatory critique more generally

In vitro controlled drug release from contact lenses materials under physiological ocular tear flow

Poster presented at the 9th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology. Lisbon, 31 March-3 April 2014.BASF; Fundação para a Ciência e a Tecnologi

Wounds research for patient benefit: a 5-year programme of research

Background Complex wounds are those that heal by secondary intention and include lower-limb ulcers, pressure ulcers and some surgical wounds. The care of people with complex wounds is costly, with care mainly being delivered by community nurses. There is a lack of current, high-quality data regarding the numbers and types of people affected, care received and outcomes achieved. Objectives To (1) assess how high-quality data about complex wounds can be captured effectively for use in both service planning and research while ensuring integration with current clinical data collection systems and minimal impact on staff time; (2) investigate whether or not a clinical register of people with complex wounds could give valid estimates of treatment effects, thus reducing dependence on large-scale randomised controlled trials (RCTs); (3) identify the most important research questions and outcomes for people with complex wounds from the perspectives of patients, carers and health-care professionals; (4) evaluate the potential contributions to decision-making of individual patient data meta-analysis and mixed treatment comparison meta-analysis; and (5) complete and update systematic reviews in topic areas of high priority. Methods To meet objectives 1 and 2 we conducted a prevalence survey and developed and piloted a longitudinal disease register. A consultative, deliberative method and in-depth interviews were undertaken to address objective 3. To address objectives 4 and 5 we conducted systematic reviews including mixed treatment comparison meta-analysis. Results From the prevalence survey we estimated the point prevalence of all complex wounds to be 1.47 per 1000 people (95% confidence interval 1.38 to 1.56 per 1000 people). Pressure ulcers and venous leg ulcers were the most common type of complex wound. A total of 195 people with a complex wound were recruited to a complex wounds register pilot. We established the feasibility of correctly identifying, extracting and transferring routine NHS data into the register; however, participant recruitment, data collection and tracking individual wounds in people with multiple wounds were challenging. Most patients and health professionals regarded healing of the wound as the primary treatment goal. Patients were greatly troubled by the social consequences of having a complex wound. Complex wounds are frequently a consequence of, and are themselves, a long-term condition but treatment is usually focused on healing the wound. Consultative, deliberative research agenda setting on pressure ulcer prevention and treatment with patients, carers and clinicians yielded 960 treatment uncertainties and a top 12 list of research priorities. Of 167 RCTs of complex wound treatments in a systematic review of study quality, 41% did not specify a primary outcome and the overall quality of the conduct and reporting of the research was poor. Mixed-treatment comparison meta-analysis in areas of high priority identified that matrix hydrocolloid dressings had the highest probability (70%) of being the most effective dressing for diabetic foot ulcers, whereas a hyaluronan fleece dressing had the highest probability (35%) of being the most effective dressing for venous ulcers; however, the quality of this evidence was low and uncertainty is high. Conclusions Complex wounds are common and costly with a poor evidence base for many frequent clinical decisions. There is little routine clinical data collection in community nursing. A prospective complex wounds register has the potential to both assist clinical decision-making and provide important research evidence but would be challenging to implement without investment in information technology in NHS community services. Future work should focus on developing insights into typical wound healing trajectories, identifying factors that are prognostic for healing and assessing the cost-effectiveness of selected wound treatments. Funding The National Institute for Health Research Programme Grants for Applied Research programme

Deep Eutectic Solvents (DES) based on sulphur for silicon surfaces as alternative lubricants

Encontro realizado na Universidade Nova de Lisboa de 24-27 de junho de 2019.Deep eutectic mixtures composed of hydrogen-bond donors and hydrogen-bond acceptors, the so-called DESs, have recently being proposed as possible “green” alternatives to mineral oils and ionic liquids (ILs) in the lubrication of steel surfaces. DESs have similar physical properties to ILs but have the advantage of being cheaper and easier to prepare. In this work, new DESs containing sulphur units in their structure were prepared and tested in the lubrication of silicon surfaces which are relevant for nano/microelectromechanical systems (NEMS/MEMS). The following new DESs were prepared: dibutil-ethyl sulfonium ethylsulfate: polyethylene glycol ([S4,4,2][EtSO4]:PEG), ethyl-tetrahydrothiophenium ethylsulfate: polyethylene glycol ([C2-THT][EtSO4]:PEG, cis-1-ethyl-3methylimidazolium canforsulfonate: polyethylene glycol ([C2MIM][(S)-CSA]:PEG), and 1,3-dimethylpiridinium methyl sulfate: polyethylene glycol ([C1-3-pic][MeSO4]:PEG). Other DES, already known, were tested for comparison purposes: tetrabutylammonium bromide: ‎tetrahydrothiophene 1,1-dioxide ([N4,4,4,4][Br]:Sulfolane), choline chloride: polyethylene glycol (ChCl:PEG), and tetrabutylammonium bromide: polyethylene glycol ([N4,4,4,4][Br]:PEG). All DESs were characterized in terms of their water content, viscosity, wettability, and tribological properties. The friction coefficients were measured in a nanotribometer using steel spheres against Si surfaces. The new DES prepared from ILs based on the sulfur-containing anions showed good tribological performance, but the best results were obtained with [C2MIM][(S)-CSA]:PEG and [C1-3-pic][MeSO4]:PEG which reduced the friction coefficients to values < 0.1, typical of excellent lubrication conditions.Fundação para a Ciência e a Tecnologia (FCT-Portugal) and COMPETE (FEDER), within projects UID/QUI/00100/2013, UID/NAN/50024/2013 and PTDC/CTM-POL/3698/2014info:eu-repo/semantics/draf

Simulation of the hydrodynamic conditions of the eye to better reproduce the drug release from hydrogel contact lenses: experiments and modeling

The final publication is available at Springer via http://dx.doi.org/10.1007/s13346-016-0303-1Currently, most in vitro drug release studies for ophthalmic applications are carried out in static sink conditions. Although this procedure is simple and useful to make comparative studies, it does not describe adequately the drug release kinetics in the eye, considering the small tear volume and flow rates found in vivo. In this work, a microfluidic cell was designed and used to mimic the continuous, volumetric flow rate of tear fluid and its low volume. The suitable operation of the cell, in terms of uniformity and symmetry of flux, was proved using a numerical model based in the Navier-Stokes and continuity equations. The release profile of a model system (a hydroxyethyl methacrylate-based hydrogel (HEMA/PVP) for soft contact lenses (SCLs) loaded with diclofenac) obtained with the microfluidic cell was compared with that obtained in static conditions, showing that the kinetics of release in dynamic conditions is slower. The application of the numerical model demonstrated that the designed cell can be used to simulate the drug release in the whole range of the human eye tear film volume and allowed to estimate the drug concentration in the volume of liquid in direct contact with the hydrogel. The knowledge of this concentration, which is significantly different from that measured in the experimental tests during the first hours of release, is critical to predict the toxicity of the drug release system and its in vivo efficacy. In conclusion, the use of the microfluidic cell in conjunction with the numerical model shall be a valuable tool to design and optimize new therapeutic drug-loaded SCLs.info:eu-repo/semantics/publishedVersio

Experimental supporting data on DIS3L2 over nonsense-mediated mRNA decay targets in human cells

In this article, we present supportive data related to the research article “A role for DIS3L2 over natural nonsense-mediated mRNA decay targets in human cells” [1], where interpretation of the data presented here is available. Indeed, here we analyze the impact of the DIS3L2 exoribonuclease over nonsense-mediated mRNA decay (NMD)-targets. Specifically, we present data on: a) the expression of various reporter human β-globin mRNAs, monitored by Northern blot and RT-qPCR, before and after altering DIS3L2 levels in HeLa cells, and b) the gene expression levels of deregulated transcripts generated by re-analyzing publicly available data from UPF1-depleted HeLa cells that were further cross-referenced with a dataset of transcripts upregulated in DIS3L2-depleted cells. These analyses revealed that DIS3L2 regulates the levels of a subset of NMD-targets. These data can be valuable for researchers interested in the NMD mechanism.This work was partially supported by Fundação para a Ciencia e a Tecnologia (FCT) (PTFC/BIM-MEC/3749/2014 to LR and UID/MULTI/04046/2013 to BioISI). PJdC, HAS and JFG-M are recipients of a fellowship from BioSys PhD programme (SFRH/BD/52495/2014, SFRH/BD/52492/2014, and PD/BD/ 142898/2018, respectively) and JM is a postdoctoral fellow (SFRH/BPD/98360/2013) from FCT. Work at ITQB-NOVA was financially supported by: Project LISBOA-01-0145-FEDER-007660 funded by the European Regional Development Fund (FEDER) through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI) and by FCT funds: PTDC/BIA-MIC/1399/2014 to CMA and PTFC/BIM-MEC/3749/2014 to SCV. SCV was financed by program IF of FCT (IF/00217/2015). MS was financed by an FCT contract according to DL57/2016 [SFRH/BPD/109464/2015]info:eu-repo/semantics/publishedVersio

Transfusion Volume for Children with Severe and LifeThreatening Anaemia

Background: Severe anaemia (haemoglobin37.5C) at screening. 30mls/kg reduced mortality in the 1943(61%) children without fever (28-day HR=0.43 (0.27,0.69) p=0.001), but increased mortality in the 1253(39%) children with fever (HR=1.91 (1.04,3.49) p=0.04). There was no evidence of differences between groups in re-admissions (p=0.38), serious adverse events (p=0.58) nor in haemoglobin recovery at 180-days (p=0.10). Conclusions: Mortality could be reduced by transfusing 30mls/kg whole blood equivalent in children presenting with severe anaemia without fever

Pilot feasibility randomized clinical trial of negative-pressure wound therapy versus usual care in patients with surgical wounds healing by secondary intention

Background Surgical wounds healing by secondary intention (SWHSI) are increasingly being treated with negative‐pressure wound therapy (NPWT) despite a lack of high‐quality research evidence regarding its clinical and cost‐effectiveness. This pilot feasibility RCT aimed to assess the methods for and feasibility of conducting a future definitive RCT of NPWT for the treatment of SWHSI. Methods Eligible consenting adult patients receiving care at the study sites (2 acute and 1 community) and with a SWHSI appropriate for NPWT or wound dressing treatment were randomized 1 : 1 centrally to receive NPWT or usual care (no NPWT). Participants were followed up every 1–2 weeks for 3 months. Feasibility (recruitment rate, time to intervention delivery) and clinical (time to wound healing) outcomes were assessed. Results A total of 248 participants were screened for eligibility; 40 (16·1 per cent) were randomized, 19 to NPWT and 21 to usual care. Twenty‐four of the 40 wounds were located on the foot. Participants received NPWT for a median of 18 (range 0–72) days. Two participants in the NPWT group never received the intervention and 14 received NPWT within 48 h of randomization. Five participants in the usual care group received NPWT during the study. Ten of the 40 wounds were deemed to have healed during the study. Conclusion A full‐scale RCT to investigate the clinical and cost‐effectiveness of NPWT for SWHSI is feasible. This study identified crucial information on recruitment rates and data collection methods to consider during the design of a definitive RCT. Registration number: ISRCTN12761776 (www.iscrtn.com