Design of non-spherical poly (lactic-co-glycolic acid) nanoparticles functionalized with hyaluronic acid for active tumor targeting

Natural polymer-based nanoparticles (NPs) have been widely investigated in the cancer therapy field thanks to their several advantages such as improved drug stability, specific delivery and reduced toxicity. In particular, NPs surface functionalized with hyaluronic acid (HA-based NPs) have been largely employed thanks to their active tumor-targeting efficiency. Besides size and composition, HA-based NPs shape plays a significant role in regulating the interaction between drug-loaded NPs and the biological environment. For these reasons, unloaded and irinotecan-loaded core-shell (IRIN) non-spherical (NS) NPs, composed of poly (lactic-co-glycolic acid) (PLGA) and coated with hyaluronic acid (HA), obtained from spherical ones, by means of film stretching method (FSM) are presented and compared with their spherical (S) analog NPs. The physicochemical characterization over time of NS and S NPs aimed at investigating variations of equivalent hydrodynamic diameter and ζ-potential by means of Dynamic Light Scattering (DLS) and Electrophoretic Light Scattering (ELS) has been employed. Furthermore, morphological analyses of the NP shapes by means of Transmission Electron Microscopy (TEM) have been performed. In addition, Differential Scanning Calorimetry (DSC) was employed to determine the polymers' assembly in HA-based NP formulations. The HA surface functionalization of NPs improves NP size stability over time thanks to both a high degree of hydration and a raised in electrostatic repulsion between NPs. In vitro release kinetics of IRIN-loaded NS and S HA-based NPs have been achieved in 300 h. Furthermore, in vitro biocompatibility and cell uptake using healthy fibroblast, L929, and human breast carcinoma cells, HS578T, were explored. In particular, a significant effect on cytotoxicity and internalization for NS HA-based NPs has been highlighted, for the synergistic effect of shape and active targeting of NS NPs if compared to S NPs. The effect could be ascribed to the active tumor-targeting ability of NS HA-based nanodevices due to morphological features (shape).