Cyclodextrin-based star polymers as a versatile platform for nanochemotherapeutics: Enhanced entrapment and uptake of idarubicin

A series of cyclodextrin-based star polymers were synthesized using β-cyclodextrin (CD) as hydrophilic core, methyl methacrylate (MMA) and tert-butyl acrylate (tBA) as hydrophobic arms. Star polymers, either homopolymers or random/block copolymers, showed narrow molecular weight distributions. Grafting hydrophobic arms created CD-based nanoparticles (CD-NPs) in the size range (130-200. nm) with narrow PdI <0.15 and slightly negative ζ-potential. Particle surface could be modified with chitosan to impart a positive surface charge. Colloidal stability of CD-NPs was a function of pH as revealed by the pH-titration curves. CD-NPs were used as carrier for the chemotherapeutic drug idarubicin (encapsulation efficiency, EE ~40%) ensuring prolonged release profile (~80% after 48. h). For cell-based studies, coumarin-6 was encapsulated as a fluorescent marker (EE ~75%). Uptake studies carried out on A549 and Caco-2 cell lines proved the uptake of coumarin-loaded NPs as a function of time and preferential localization in the cytoplasm. Uptake kinetics revealed no saturation or plateau over 6. h. Chitosan-modified NPs showed significantly improved, concentration-dependent cellular uptake. Meanwhile, CD-NPs were non-cytotoxic on both cell lines over the concentration range (0.25-3. mg/ml) as studied by MTT and LDH assays. In conclusion, CD star polymers can be considered a versatile platform for a new class of biocompatible nanochemotherapy.