Biodegradable paclitaxel-loaded microparticles prepared from novel block copolymers: influence of polymer composition on drug encapsulation and release.

This study covers the preparation of microspheres for the controlled and targeted release of paclitaxel, using novel degradable polymers as carrier materials. Paclitaxel-loaded microspheres were prepared by oil-in-water single-emulsion solvent extraction/evaporation technique by using a series of polyurethanes and a block copolymer; the physicochemical properties of these polymers were modulated by changing nature and composition of their structural units. The obtained microparticles showed a regular morphology and properties (diameter: 1-100 µm; resuspension index: 18.8-100%; encapsulation efficiency: 26.6-97.2%) depending on polymer hydrophilicity and emulsifier used. In vitro release curves showed in all cases almost zero-order kinetics after an initial low burst effect (from 1 to 8.4%), which is required to minimize the drug side effects. This work also proposes a novel strategy to combine a controlled and a targeted release through the functionalization of the polymer matrix with peptide sequences. An RGD-functionalized polyurethane was used to successfully prepare paclitaxel-loaded microparticles. Studies on the preparation of polymer microspheres are reported.

PAM-microfabricated polyurethane scaffolds: in vivo and in vitro preliminary studies.

Polymeric scaffolds were realised with linear degradable PU in the form of square, hexagonal and octagonal grids. They were characterised in terms of their mechanical properties. Analysis shows that the mechanical properties of the scaffolds depend on their geometries which are easily modulated using PAM. In vitro biological assays showed that PU promotes the adhesion and proliferation of fibroblast cells and that cell activities are better on PU scaffolds than on PU films. In vivo implantation of PU and PLGA scaffolds and PU films demonstrated that the scaffolds are completely resorbed after three months with a slight inflammatory response, while the PU film was still present after six months with an intense granulomatous reaction.

A new D-dimer cutoff in bedridden hospitalized elderly patients.

Asymptomatic deep vein thrombosis (DVT) and pulmonary embolism are leading causes of morbidity following the hospitalization of elderly people. The diagnosis of DVT is supported by the D-dimer laboratory assay. The concentration of D-dimer increases in patients with DVT, but may be high in other conditions too (i.e. cancer, infections and inflammation). Old age coincides with a physiological increase in D-dimer values, and that is why D-dimer assay in the elderly is characteristically highly sensitive but scarcely specific. The aim of our study was to explore the reliability of different D-dimer cutoffs for the diagnosis of asymptomatic DVT in a population of bedridden hospitalized elderly patients. We studied 199 patients who were a mean 86.3 ±â€Š6.7 years old. All participants underwent lower limb Doppler ultrasound (DUS) and D-dimer venous blood sampling on admission. In our cohort, the usual cutoff proved highly sensitive (100%), but its specificity was very poor (20.1%). To find a higher cutoff that could improve the method's specificity, we analyzed our data using a receiver operating characteristic curve analysis. The resulting D-dimer cutoff of 492 µg/l enabled us to retain the same sensitivity while improving the test's specificity to 39.1%, with a consequent improvement in its positive predictive value and accuracy. In addition to improving the method's reliability, this result may be helpful in clinical practice, in both medical wards and nursing homes. By adopting a cutoff of 492 µg/l, clinicians could significantly increase the proportion of older patients in whom DVT can be safely ruled out, reducing referrals for DUS and administration of heparin, with consequent clinical, practical and economic advantages.

Poly(ester urethane) guides for peripheral nerve regeneration.

A biocompatible and elastomeric PU was synthesized from low-molecular-weight PCL as macrodiol, CMD as chain extender and HDI as chain linker for applications in the field of peripheral nerve repair. PU cast films supported in vitro attachment and proliferation of NOBEC. The in vitro adhesion and proliferation of S5Y5 neuroblastoma cells on the inner surface of uncoated, gelatin- and PL-coated PU guides were compared. Due to their superior in vitro performance, PL-coated PU guides were tested in vivo for the repair of 1.8 cm-long defects in rat sciatic nerves. The progressive regeneration was confirmed by EMG and histological analysis showing the presence of regenerating fibers in the distal stumps.