The preparation of pH and GSH dual responsive thiolated heparin/DOX complex and its application as drug carrier. (15th February 2020)

• Record Type: Journal Article
• Authors: wen, Juan; Chen, Qingping; Ye, Lin; Zhang, Huan; Zhang, Aiying; Feng, Zengguo
• Is Part Of: Carbohydrate polymers. Volume 230(2020)
• Publication Date: 2020-02-15
• Subjects: Heparin -- Polyion complex -- Stability -- Dual sensitive drug release -- Doxorubicin; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2019.115592
• Languages: English
• ISSNs: 0144-8617

Abstract

Highlights: The use of heparin can guarantee drug carrier's biocompatibility and bio-safety. Heparin based polyion can significantly simplify drug carrier's preparation. In vitro and in vivo stabilities are greatly enhanced by heparin's crosslinking. Heparin/DOX drug carrier possesses pH and GSH dual responsive drug release. The carrier exhibits excellent in vitro and in vivo anti-tumor performance. 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.