Cyclic nigerosyl-1,6-nigerose-based nanosponges: An innovative pH and time-controlled nanocarrier for improving cancer treatment

• Published in: Carbohydrate polymers 2018-08, Vol.194, p.111-121
• Main Authors: Caldera, F., Argenziano, M., Trotta, F., Dianzani, C., Gigliotti, L., Tannous, M., Pastero, L., Aquilano, D., Nishimoto, T., Higashiyama, T., Cavalli, R.
• Format: Article
• Language: English
• Subjects: CNN; Doxorubicin; Nanosponges; Nigerose; Sustained release
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2018.04.027

•New tetraglucose-based biomaterial, comprising cyclic nigerosyl-1-6-nigerose (CNN).•Cross-linked nanoparticles, named CNN-nanosponges, for doxorubicin delivery.•pH-dependent and prolonged release kinetics of doxorubicin from CNN-nanosponges.•In vitro enhanced anticancer activity of doxorubicin-loaded nanosponges. The design and structural optimisation of a novel polysaccharide-based nanomaterial for the controlled and sustained release of doxorubicin are here reported. A cross-linked polymer was obtained by reacting a tetraglucose, named cyclic nigerosyl-1-6-nigerose (CNN), with pyromellitic dianhydride. The cross-linking reaction formed solid nanoparticles, named nanosponges, able to swell as a function of the pH. Nanoparticle sizes were reduced using High Pressure Homogenization, to obtain uniform nanosuspensions. Doxorubicin was incorporated into the CNN-nanosponges in a good extent. DSC and solid state NMR analyses proved the drug interaction with the polymer matrix. In vitro studies demonstrated pH-dependent slow and prolonged release kinetics of the drug from the nanoformulation. Doxorubicin-loaded CNN-nanosponges were easily internalized in A2780 cell line. They might considered an intracellular doxorubicin reservoir, able to slowly release the drug over time. CNN-nanosponges may be promising biocompatible nanocarriers for the sustained delivery of doxorubicin with potential localised application in cancer treatments.