Fabrication of doxorubicin and heparin co-loaded microcapsules for synergistic cancer therapy

In this study, a layer-by-layer (LbL) assembly (HEP/CHI)5 microcapsule with doxorubicin hydrochloride (DOX) encapsulating inside was fabricated via alternatively depositing heparin (HEP) and chitosan (CHI) onto DOX-loaded CaCO3 templates. The microcapsules were of stable architecture and had good dispersity in aqueous medium. Fluorescence observation showed that DOX distributed both in the wall and in the cavity of microcapsules, while HEP presented in the capsule wall. The release rate of DOX increased at acidic pH as compared with that at basic pH, suggesting a pH-responsive drug release behavior. The microcapsules with positively charged CHI lying on the outer layer could protect HEP from heparanase degradation and achieve intracellular co-delivery of both DOX and HEP. Thus, the DOX-loaded microcapsules could have improved inhibition activity against A549 cells by combining pharmacological actions of DOX and HEP.