Synthesis of hyaluronic acid-based polymersomes for doxorubicin delivery to metastatic breast cancer

In the current research, the synthesis of polysaccharide-based polymersomes for targeted delivery of doxorubicin is reported. To this aim, doxorubicin was encapsulated in aqueous compartment of hyaluronan-polycaprolactone polymersomes via nanoprecipitation method. Then the therapeutic index of the prepared formulation was studied in metastatic breast cancer model in vitro and in vivo. The size of obtained polymersomes was 146.2 +/- 9.6 nm and offered the efficiency of encapsulation and the content of loading %54.9 +/- 4.0 and %3.6 +/- 0.4, respectively. The obtained results exhibited that the HA-PCL polymersomes controlled the release of DOX in a sustained manner. Then, the CD44-receptor mediated endocytosis through hyaluronan shell of the prepared formulation was confirmed in murine 4T1 and human MCF-7 cancer cell lines implementing flow cytometry and MTT assays. Much better in vivo antitumor efficacy and wider tumor tissue necrosis and better bio-distribution features of this formulation in comparison with PEG-PCL-DOX nanoparticles suggested that HA-PCL-DOX can potentially reduce off-target effects due to its targeting capability.