PLA-PCL-PEG-PCL-PLA based micelles for improving the ocular permeability of dexamethasone: development, characterization, and in vitro evaluation.

The aim of the present research was to investigate the feasibility of developing polylactide-polycaprolactone-polyethylene glycol-polycaprolactone-polylactide (PLA-PCL-PEG-PCL-PLA) based micelles to improve ocular permeability of dexamethasone (DEX). PLA-PCL-PEG-PCL-PLA copolymers were synthesized by a ring-opening polymerization method. DEX was loaded into the developed copolymers. The DEX-loaded micelles were characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS) methods. Cytotoxicity of the micelles obtained was investigated on L929 cell line. Cellular uptake was followed by fluorescence microscopy and flow cytometry analyses. The release behavior of DEX from the micelles as well as the drug release kinetics was studied. Corneal permeability was also evaluated using an ex vivo bovine model. The pentablock copolymers were successfully synthesized. The TEM results verified the formation of spherical micelles, the sizes of which was approximately 65 nm. The micelles exhibited suitable compatibility on L929 cells. The release profile showed an initial burst release phase followed by a sustained release phase, the kinetic of which was close to the Weibull's distribution model. The micelles showed higher corneal permeability in comparison to a marketed DEX eye drop. Taken together, the results indicated that the PLA-PCL-PEG-PCL-PLA micelles could be appropriate candidates for the ocular delivery of DEX, and probably other hydrophobic drugs.

Ultrasound-guided hematoma block in distal radial fracture reduction: a randomised clinical trial.

OBJECTIVE: We compared the efficacy and safety of ultrasound-guided haematoma block with that of procedural sedation and analgesia in patients with acute distal radial fracture reduction pain control. METHODS: This was a randomised clinical trial on adult patients conducted in two teaching hospitals. Patients received intravenous midazolam plus fentanyl in the procedural sedation and analgesia group, and fracture site injection of lidocaine 10% in the ultrasound guided haematoma block group. We measured pain scores before reduction, during reduction and 5, 10 and 15 min after reduction by a numeric rating scale, and patient and physician satisfaction by a four-level Likert scale. Time to discharge, early adverse effects and late complications were also compared. RESULTS: We enrolled 160 patients with distal radial fracture and randomised 143 patients into two groups (after excluding 17 patients). Pain was effectively controlled in both groups. Pain scores had no statistically significant difference before and during reduction and 5 and 15 min after reduction in the procedural sedation and analgesia and ultrasound guided haematoma block groups. Patient and physician overall satisfaction were similar in the two groups. Time to discharge was significantly lower in the ultrasound guided haematoma block group. Four patients (5.5%) in the procedural sedation and analgesia group showed early adverse effects. No patient in either group showed any late complications. CONCLUSIONS: Ultrasound guided haematoma block may be a safe and effective alternative to procedural sedation and analgesia. TRIAL REGISTRATION NUMBER: 201112308104N5.