The preparation and morphology control of heparin-based pH sensitive polyion complexes and their application as drug carriers

• Published in: Carbohydrate polymers Vol. 211; pp. 370 - 379
• Main Authors: Li, Qingxuan, Ye, Lin, Zhang, Aiying, Feng, Zengguo
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2019
• Subjects: DOX; Drug carrier; Heparin; pH sensitivity; Polyion complex; Drug carrier; Heparin; DOX; pH sensitivity; Polyion complex
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2019.01.089

[Display omitted] •Heparin is a versatile building block to construct biomedical polyion complex(PIC).•PIC’s morphologies are tuned from micelle to vesicle by heparin content.•The PIC drug carrier with high DLC is prepared by very simple manipulation.•pH sensitive release is spontaneously endowed without additional modification.•Heparin PIC drug carrier has significant cytotoxicity against tumor cell in vitro. Heparin as negative polysaccharide is a universal building block to form polyion complex with different cationic counterparts. In this paper, three different cations, including chitosan, benzyldodecyldimethyl ammonium bromide and doxorubicin hydrochloride, were used to prepare heparin-based polyion complexes (HPICs). Their morphologies could be tuned by heparin content in HPIC, and they also showed pH-sensitive decomposition. Doxorubicin was further encapsulated into micelle and vesicle carrier made from heparin-benzyldodecyl dimethyl ammonium bromide PIC, whereas heparin-doxorubicin PIC could be directly used as drug carrier. In vitro drug release proved the drug carriers exhibit obvious pH sensitive release behaviour. Cytotoxicity indicated the drug carrier possessed significant cytotoxicity to tumor cells. The cell uptake observed by CLSM showed the carrier was able to deliver antitumor drug into tumor cell’s nucleus. Consequently, these results showed the promising potential of HPIC in drug carrier application.