Carbon Nanotubes as Nanocarriers for N-Bencenesulfonyl of Heterocycles

Otro; IV Reunión Internacional de Ciencias Farmacéuticas (RICiFa); 2016

Chagas disease, an infection caused by the protozoan Trypanosoma cruzi, remains endemic in Latin America, though it is actually widespread in many other continents. Although benznidazole (BNZ) is selected as first-line therapy, safer and more effective trypanocidal drugs are needed. As part of our ongoing project on new antiparasitic agents, we prepared a series of N-benzenesulfonyl derivatives of heterocycles (BS-Het), which have significant trypanocidal activity but low aqueous solubility. Among the strategies to enhance solubility of drugs through the use of nanocarriers, functionalized carbon nanotubes (f-CNTs) have sparked significant interest. This work aims at reporting the functionalization of CNTs with PEG-5000 monomethylether (CNT-PEG) to improve their biocompatibility and dispersibility, and the preliminary studies on loading and releasing of BNZ, N-benzenesulfonyl-benzimidazole (BS-BZD) and N-benzenesulfonyl-1,2,3,4-tetrahydroquinoline (BS-THQ) onto f-CNTs.Functionalization of CNTs was achieved by carboxylation with concentrated HNO3 and H2SO4 acids in 3:1 volume ratio (CNT-COOH). Acid-treated CNTs were esterified with PEG-5000 in water in the presence of carbonyldiimidazole as catalyst. The characterization of f-CNTs was performed by FT-IR and SEM. Quantification of acid groups by titration showed 0.86 mmol/g for CNT-COOH, and 0.38 mmol/g for CNT-PEG, indicating 55% of esterification. Dispersion in water of CNT-COOH and CNT-PEG was improved and found to be dependent on pH. Loading of compounds onto f-CNTs were done by mixing them in a water/ethanol solution for 24h at room temperature. Loading capacities were 7% (BNZ), 27% (BS-BZD) and 21% (BS-THQ). To evaluate the release, samples were immersed in buffer PBS and the amount released was determined by UV-Vis, finding that 22% (BNZ), 26% (BS-BZD) and 23% (BS-THQ) were liberated in 24h at 37°C. To summarize, f-CNTs showed to be able to adsorb poorly soluble BS-Het and release them in biocompatible media, opening a new window for improving their solubility and continue their drug development process.