Cyclodextrin enhances corneal tolerability and reduces ocular toxicity caused by diclofenac

With advances in refractive surgery and demand for cataract removal and lens replacement, the ocular use of nonsteroidal anti-inflammatory drugs (NSAIDs) has increased. One of the most commonly used NSAIDs is diclofenac (Diclo). In this study, cyclodextrins (CDs), α-, β-, γ-, and HP-β-CDs, were investigated with in vitro irritation and in vivo ulceration models in rabbits to reduce Diclo toxicity. Diclo-, α-, β-, γ-, and HP-β-CD inclusion complexes were prepared and characterized and Diclo-CD complexes were evaluated for corneal permeation, red blood cell (RBCs) haemolysis, corneal opacity/permeability, and toxicity. Guest- (Diclo-) host (CD) solid inclusion complexes were formed only with β-, γ-, and HP-β-CDs. Amphipathic properties for Diclo were recorded and this surfactant-like functionality might contribute to the unwanted effects of Diclo on the surface of the eye. Contact angle and spreading coefficients were used to assess Diclo-CDs in solution. Reduction of ocular toxicity 3-fold to16-fold and comparable corneal permeability to free Diclo were recorded only with Diclo-γ-CD and Diclo-HP-β-CD complexes. These two complexes showed faster healing rates without scar formation compared with exposure to the Diclo solution and to untreated groups. This study also highlighted that Diclo-γ-CD and Diclo-HP-β-CD demonstrated fast healing without scar formation

Raman-active modes in defective peapod

International audienceThe vibrational properties of defective single-walled carbon nanotube filled with C60 fullerene is the subject of the current study. For this aim we use the spectral moments method in the framework of the bond-polarization theory to calculate the nonresonant Raman spectra of hexa-vacancy defective C60 peapods. Essentially, the vibrational properties are closely coupled with the atomic structure of the system. The evolution of the Raman spectrum as a function of the spatial arrangement of defects in carbon nanotubes is discussed. This work provides benchmark theoretical results to understand the experimental data of defective C60 peapod

VoroCrust: Voronoi Meshing Without Clipping

Polyhedral meshes are increasingly becoming an attractive option with particular advantages over traditional meshes for certain applications. What has been missing is a robust polyhedral meshing algorithm that can handle broad classes of domains exhibiting arbitrarily curved boundaries and sharp features. In addition, the power of primal-dual mesh pairs, exemplified by Voronoi-Delaunay meshes, has been recognized as an important ingredient in numerous formulations. The VoroCrust algorithm is the first provably-correct algorithm for conforming polyhedral Voronoi meshing for non-convex and non-manifold domains with guarantees on the quality of both surface and volume elements. A robust refinement process estimates a suitable sizing field that enables the careful placement of Voronoi seeds across the surface circumventing the need for clipping and avoiding its many drawbacks. The algorithm has the flexibility of filling the interior by either structured or random samples, while preserving all sharp features in the output mesh. We demonstrate the capabilities of the algorithm on a variety of models and compare against state-of-the-art polyhedral meshing methods based on clipped Voronoi cells establishing the clear advantage of VoroCrust output.Comment: 18 pages (including appendix), 18 figures. Version without compressed images available on https://www.dropbox.com/s/qc6sot1gaujundy/VoroCrust.pdf. Supplemental materials available on https://www.dropbox.com/s/6p72h1e2ivw6kj3/VoroCrust_supplemental_materials.pd

Self-learning Kinetic Monte-Carlo method: application to Cu(111)

We present a novel way of performing kinetic Monte Carlo simulations which does not require an {\it a priori} list of diffusion processes and their associated energetics and reaction rates. Rather, at any time during the simulation, energetics for all possible (single or multi-atom) processes, within a specific interaction range, are either computed accurately using a saddle point search procedure, or retrieved from a database in which previously encountered processes are stored. This self-learning procedure enhances the speed of the simulations along with a substantial gain in reliability because of the inclusion of many-particle processes. Accompanying results from the application of the method to the case of two-dimensional Cu adatom-cluster diffusion and coalescence on Cu(111) with detailed statistics of involved atomistic processes and contributing diffusion coefficients attest to the suitability of the method for the purpose.Comment: 18 pages, 9 figure

Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations : design, characterisation, toxicity and transcorneal permeation studies

This study was aimed at preparing, characterising and evaluating in situ gel formulations based on a blend of two hydrophilic polymers i.e. poloxamer 407 (P407) and poloxamer 188 (P188) for a sustained ocular delivery of ketorolac tromethamine (KT). Drug-polymer interaction studies were performed using {DSC} and FT-IR. The gelation temperature (Tsol-gel), gelation time, rheological behaviour, mucoadhesive characteristics of these gels, transcorneal permeation and ocular irritation as well as toxicity was investigated. {DSC} and FT-IR studies revealed that there may be electrostatic interactions between the drug and the polymers used. {P188} modified the Tsol/gel of {P407} bringing it close to eye temperature (35°C) compared with the formulation containing {P407} alone. Moreover, gels that comprised {P407} and {P188} exhibited a pseudoplastic behaviour at different concentrations. Furthermore, mucoadhesion study using mucin discs showed that in situ gel formulations have good mucoadhesive characteristics upon increasing the concentration of P407. When comparing formulations {PP11} and PP12, the work of adhesion decreased significantly (P < 0.001) from 377.9 ± 7.79 mN.mm to 272.3 ± 6.11 mN.mm. In vitro release and ex vivo permeation experiments indicated that the in situ gels were able to prolong and control {KT} release as only 48 of the {KT} released within 12 h. In addition, the HET-CAM and {BCOP} tests confirmed the non-irritancy of {KT} loaded in situ gels, and HET-CAM test demonstrated the ability of ocular protection against strongly irritant substances. {MTT} assay on primary corneal epithelial cells revealed that in situ gel formulations loaded with {KT} showed reasonable and acceptable percent cell viability compared with control samples