Synthesis of hyaluronic acid core-shell nanoparticles via simple microfluidic-assisted nanoprecipitation method for active tumor targeting

Abstract

The control of the physicochemical properties of hyaluronic acid core-shell nanoparticles (HA-based NPs) is a suitable strategy to achieve the high reproducibility of biological assays. In particular, the active targeting efficiency of HA-based NPs is a key point for the cancer treatment. This opens a way for the employment of microfluidic technology to overcome the drawbacks related to the synthesis of NPs by means of traditional bulk methods such as lower drug encapsulation efficiency and consequently a lower cancer cell killing effect. For these reasons, blank and irinotecan-loaded HA-based NPs, without any chemical modifications, were synthesized by means of a simple and fast microfluidic method (MM) and compared with those synthesized by the bulk method (BM). In particular, their aggregation behavior and morphology were investigated by dynamic light scattering, ζ-potential, and transmission electron microscopy. The drug encapsulation efficiency and irinotecan kinetic release of irinotecan-loaded HA-based NPs synthesized by both MM and BM were evaluated. All NP formulations synthesized by MM present smaller size, narrower size distribution, controlled morphology, higher yield, and higher drug encapsulation efficiency than those synthesized by BM. Furthermore, the biological assays based on the in vitro biocompatibility and cell uptake using HS578T, human breast carcinoma cells, and L929 cells (healthy fibroblast) were investigated, respectively. In particular, biological assays showed higher cytotoxicity and a higher internalization for HA-based NPs synthesized by MM than those synthesized by BM. Thus, the synthesis of HA-based NPs, without any polymer chemical modifications, by means of new microfluidic technology is demonstrated to be a more effective approach for the cancer treatment.