Microfluidic-Assisted Formulation of ε-Polycaprolactone Nanoparticles and Evaluation of Their Properties and In Vitro Cell Uptake.

The nanoprecipitation method was used to formulate ε-polycaprolactone (PCL) into fluorescent nanoparticles. Two methods of mixing the phases were evaluated: introducing the organic phase into the aqueous phase dropwise and via a specially designed microfluidic device. As a result of the nanoprecipitation process, fluorescein-loaded nanoparticles (NPs) with a mean diameter of 127 ± 3 nm and polydispersity index (PDI) of 0.180 ± 0.009 were obtained. The profiles of dye release were determined in vitro using dialysis membrane tubing, and the results showed a controlled release of the dye from NPs. In addition, the cytotoxicity of the NPs was assessed using an MTT assay. The PCL NPs were shown to be safe and non-toxic to L929 and MG63 cells. The results of the present study have revealed that PCL NPs represent a promising system for developing new drug delivery systems.

Fluorosurfactants for medical nanoemulsions, their surface-active and biological properties.

Nano- and microemulsions have found various applications in pharmaceutical and medical areas both in research field as well as in applied solutions for drug delivery or diagnostic agents. However, production of stable and bio- / hemocompatible nanoemulsions are still challenging. New group of ionic surfactants have been synthesized with perfluorohexyl- or perfluorooctyl-groups as hydrophobic tail. The CMC and the parametres of the O/W emulsion (the particle size distribution and the zeta-potential) were determined. The influence of the surfactants on in vitro proliferation of human endothelial cell lines HMEC-1, murine fibroblasts L929 and hemolysis were investigated as characteristic for biocompatibility. Three candidates of surfactants were selected for pre-clinical tests on a small animal model (adult Sprague Dawley rats) on the basis of preliminary studies. This allowed to obtain nanoemulsions with narrow droplets size (average droplet diameter 141-147 nm with PDI index 0.059 - 0.065) and showed better stability over time in comparison to the commercially available surfactants. Neither cytotoxic nor hemolytic potential were observed during incubation of obtained fluorosurfactans with model cell lines L929 and HMEC-1 (average cell viability above 85 % after incubation with 1% solutions) and erythrocytes (hemolysis rate below 3.1 % for all 0.5 % solutions). During acute toxicity test on rat model, it was found that all three tested surfactant solutions showed no significant differences in controlled parameters and survival rate with control group (p > 0.05). Presented surfactants are dedicated but not limited to emulsification of organic fluorocompounds.

At Long Last: Olefin Metathesis Macrocyclization at High Concentration.

Macrocyclic lactones, ketones, and ethers can be obtained in the High-Concentration Ring-Closing Metathesis (HC-RCM) reaction in high yield and selectivity at concentrations 40 to 380 times higher than those typically used by organic chemists for similar macrocyclizations. The new method consists of using tailored ruthenium catalysts together with applying vacuum to distill off the macrocyclic product as it is formed by the metathetical backbiting of oligomers. Unlike classical RCM, no large quantities of organic solvents are used, but rather inexpensive nonvolatile diluents, such as natural or synthetic paraffin oils. Moreover, use of a protecting atmosphere or a glovebox is not needed, as the new catalysts are perfectly moisture and air stable. In addition, some other cyclic compounds previously reported as unobtainable by RCM in neat conditions, or in high dilutions even, can be formed with the help of the HC-RCM method.