Multiple polysaccharide–drug complex-loaded liposomes: A unique strategy in drug loading and cancer targeting

•A complex of a cationic drug and anionic biodegradable polymer improved drug loading capacity.•The complex could be used for chemotherapeutic applications.•Hybrid liposome co-loaded with polysaccharide drug complex enhanced the anticancer effect.•The ratiometric combination of doxorubicin and cispl...

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Bibliographic Details
Published in:Carbohydrate polymers 2017-10, Vol.173, p.57-66
Main Authors: Ruttala, Hima Bindu, Ramasamy, Thiruganesh, Gupta, Biki, Choi, Han-Gon, Yong, Chul Soon, Kim, Jong Oh
Format: Article
Language:English
Subjects:
Cisplatin
Dextran sulfate
Doxorubicin
Liposome
Sodium alginate
Transferrin
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Summary:•A complex of a cationic drug and anionic biodegradable polymer improved drug loading capacity.•The complex could be used for chemotherapeutic applications.•Hybrid liposome co-loaded with polysaccharide drug complex enhanced the anticancer effect.•The ratiometric combination of doxorubicin and cisplatin induced apoptosis. In the present study, a unique strategy was developed to develop nanocarriers containing multiple therapeutics with controlled release characteristics. In this study, we demonstrated the synthesis of dextran sulfate-doxorubicin (DS-DOX) and alginate-cisplatin (AL-CIS) polymer–drug complexes to produce a transferrin ligand-conjugated liposome. The targeted nanoparticles (TL-DDAC) were nano-sized and spherical. The targeted liposome exhibited a specific receptor-mediated endocytic uptake in cancer cells. The enhanced cellular uptake of TL-DDAC resulted in a significantly better anticancer effect in resistant and sensitive breast cancer cells compared to that of the free drugs. Specifically, DOX and CIS at a molar ratio of 1:1 exhibited better therapeutic performance compared to that of other combinations. The combination of an anthracycline-based topoisomerase II inhibitor (DOX) and a platinum compound (CIS) resulted in significantly higher cell apoptosis (early and late) in both types of cancer cells. In conclusion, treatment with DS-DOX and AL-CIS based combination liposomes modified with transferrin (TL-DDAC) was an effective cancer treatment strategy. Further investigation in clinically relevant animal models is warranted to prove the therapeutic efficacy of this unique strategy.
ISSN:0144-8617
1879-1344
DOI:10.1016/j.carbpol.2017.05.062