Abstract
Cancer therapies started to take a big advantage from new nanomedicines on the market. Since then, research tried to better understand how to maximize efficacy whilst maintaining a high safety profile. Polyethylene glycol (PEG), the gold standard for nanomedicines coating design, although in many cases is a winning choice to ensure a long circulation and colloidal stability, in other cases cause, after the first administration, the development in patients of PEG directed immunoglobulins. The phenomenon, called ABC effect, has been studied and correlated with clinical failure because of the premature removal from the circulation by immune mechanism. Therefore, alternatives to PEG need to be found. Here, looking at the backbone structural analogy, the hydrophilicity, flexibility and its GRAS status, the natural polysaccharide Inulin (INU) was investigated as PEG alternative. In particular, the first family of Inulin-g-poly-D,L-lactide amphiphilic copolymers (INU-PLAs) was synthesized. The new materials were fully characterized from the physic-chemical point of view (solubility, 1D and 2D NMR, FT-IR, UV-Vis, GPC, DSC) and showed interesting hybrid properties compared to precursors. Moreover, their ability in forming stable colloids and to serve as a carrier for doxorubicin were investigated and compared with the already well known and well characterized PEGylated counterpart, polyethylene glycol-g-poly-D,L-lactide (PEG-PLA). This preliminary investigation showed INU-PLA to be able to assemble in nanostructures less than 200 nm in size and capable of loading doxorubicin with an encapsulation efficiency in the same order of magnitude of PEG-PLA analogues.