Complementary mass spectrometric approaches and scanning electron microscopy to study the structural stability of polyurethane tunneled dialysis catheters after exposure to ethanol solutions.

RATIONALE: Ethanol lock is an emerging therapeutic option for preventing and/or controlling catheter-associated infection. A previous study of silicone catheters showed they underwent no polymer degradation when kept in 60% ethanol for 15 days at 37 °C. The stability of the more widely used polyurethane catheters was studied here in the same way. METHODS: A qualitative and quantitative study of the stability of Carbothane® catheters was performed following their immersion at 37 °C in different solvents (0.9% sodium chloride as control medium and 40%, 60%, 95% ethanol solutions) for different periods of time (from 5 min to 15 days) using scanning electron microscopy and complementary mass spectrometry techniques. RESULTS: Electron ionization analysis of the 95% ethanol storage solutions revealed the release of about 45 products (8 of which were major) subdivided into two groups according to their fragmentation patterns. Combining all the mass spectrometric data made it possible to propose structures. Group I (major) originated from the polycarbonate diol component (soft segment) and group II (minor) from the dicyclohexylmethane-4,4'-diisocyanate component (rigid segment). Semi-quantitative gas chromatography/mass spectrometry (GC/MS) analysis showed that no significantly higher release was observed after immersion for 30 min at 37 °C in 40% ethanol (mean ratio = 0.677 ± 0.068) than after immersion in reference 0.9% sodium chloride solution for 15 days (0.837 ± 0.127). CONCLUSIONS: A 30 min-40% (v/v) ethanol solution can be considered as safe for preventing the infectious complications of Carbothane® dialysis catheters, and a 30 min-60% (v/v) ethanol treatment can be occasionally used to eradicate established biofilm.

Spacer optimization of new conjugates for a melanoma-selective delivery approach.

In the search for more selective anticancer drugs, we designed and synthesized seven conjugates varying the structure of the linker connecting the 5-iodo-2'-deoxyuridine (IUdR) to the ICF 01012 melanoma-carrier for potential intratumoural specific drug release. Chemical and in vitro metabolic stability evaluations showed that, except for the ester conjugate (1), the ketal (2b), acetal (2a), carbonate (4) and carbamate (3) conjugates were compatible with our approach. The acetal (2a) and its PEGylated derivative (2c) were of particular interest for further in vivo development owing to their respective pH-dependent stability and limited metabolic degradation in order to exploit the acidic subcellular environment of malignant melanocytes to trigger the release of therapeutics upon internalization in cells.