Physicochemical and drug diffusion analysis of rifampicin containing polyethylene glycol-poly(epsilon-caprolactone) networks designed for medical device applications

This study reports the physicochemical and drug diffusion properties of rifampicin containing poly(epsilon-caprolactone) (PCL)/polyethylene glycol (PEG) networks, designed as bioactive biomaterials. Uniquely, the effects of the states of both rifampicin and PEG and the interplay between these components on these properties are described. PCL matrices containing rifampicin (1-5%, w/w) and PEG 200 (0-15%, w/w) were prepared by casting from an organic solvent (dichloromethane). The films were subsequently characterized in terms of their thermal/thermorheological, surface and tensile properties, biodegradation and drug diffusion/release properties. Incorporation of PEG and/or rifampicin significantly affected the tensile and surface properties of PCL, lowering the ultimate tensile strength, % elongation at break, Young modulus and storage and loss moduli. Both in the absence and presence of PEG, solubilisation of rifampicin within the crystalline domains of PCL was observed. PEG was present as a dispersed liquid phase. The release of rifampicin (3% loading) was unaffected by the presence of PEG. Similarly the release of rifampicin (5%) was unaffected by low concentrations of PEG (5-10%) however, at higher loadings, the release rate of rifampicin was enhanced by the presence of PEG. Rifampicin release (10% loading) was enhanced by the presence of PEG in a concentration dependent fashion. These observations were accredited to enhanced porosity of the matrix. In all cases, diffusion-controlled release of rifampicin occurred which was unaffected by polymer degradation. This study has uniquely illustrated the effect of hydrophilic pore formers on the physicochemical properties of PCL. Interestingly, enhanced diffusion controlled release was only observed from biomaterials containing high loadings of PEG and rifampicin (5, 10%), concentrations that were shown to affect the mechanical properties of the biomaterials. Care should therefore be shown when adopting this strategy to enhance release of bioactive agents from biomaterials. (C) 2011 Elsevier B.V. All rights reserved.

Management of Barrett's esophagus in the UK: Overtreated and underbiopsied but improved by the introduction of a national randomized trial

OBJECTIVES: To assess the variation in practice of Barrett's esophagus (BE) management in comparison with accepted international guidelines before and after the introduction of a large BE randomized controlled trial (RCT) with protocols including those of tissue sampling.
DESIGN: A validated anonymized questionnaire was sent to 401 senior attending gastroenterologists asking for details of their current management of BE, especially histological sampling. Of the 228 respondents, 57 individuals (each from a different center) were in the first group to enter the ASPirin Esomeprazole (BE) Chemoprevention Trial (AspECT), and we assessed change in practice in these centers.
RESULTS: Ninety percent of specialists did not take adequate biopsies for histological diagnosis. Furthermore, 74% would consider aggressive surgical resection for prevalent cases of high-grade dysplasia in BE as their first-line choice despite the associated perioperative mortality. Ninety-two percent claim their lack of adherence to guidelines is because there is a need for stronger evidence for surveillance and medical interventions. Effect of the AspECT trial: Those clinicians in centers where the AspECT trial has started have improved adherence to ACG guidelines compared with their previous practice (P < 0.05). BE patients now get 18.8% more biopsies compared with previous practice, and 37.7% if the patient is entered into the AspECT trial (P < 0.01).
CONCLUSIONS: This large study indicates both wide variation in practice and poor compliance with guidelines. Because optimal histology is arguably the most important facet of BE management, the improvement in practice in centers taking part in the AspECT trial indicates an additional value of large international RCTs.