The preparation of pH and GSH dual responsive thiolated heparin/DOX complex and its application as drug carrier

Abstract

The complicated preparation procedure and carrier's suspicious biocompatibility are two major limitations for traditional drug carrier. In this manuscript, a novel polyion complex (PIC) was prepared by simply mixing two biocompatible components, thiolated heparin and doxorubicin (DOX), and subsequently crosslinking under atmosphere, so that it can overcome the above limitations. The PIC's particle size kept stable for one week storage in PBS, and the particles wouldn't decomposed by the dilution, indicating excellent storage and anti-dilution stability resulting from the crosslinking. The PIC can release the larger amount of DOX in acidic environment than psychological environment, and largest amount in acidic and glutathione (GSH) environment, showing the pH and GSH dual sensitive drug release behavior. Furthermore, the PIC exhibited obvious tumor inhibition effect in vivo as well as long circulation ability and low heart toxicity by anti-tumor tests on tumor-bearing mice. Consequently, as-prepared PIC shows promising potential in drug carrier application.

Keywords: Doxorubicin; Dual sensitive drug release; Heparin; Polyion complex; Stability.